quetiapine-fumarate and Psychotic-Disorders

Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood.. To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP.. We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs).. We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, -4.81; 95% CI, -5.39, -4.24) and clozapine (SMD, -4.25; 95% CI, -5.24, -3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, -0.69; 95% CI, -1.35, -0.02), pimavanserin (SMD, -0.01; 95% CI, -0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, -0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo.. In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.

Topics: Antipsychotic Agents; Clozapine; Humans; Network Meta-Analysis; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Quetiapine has varied dose ranges and immediate-(QTP-IR) and extended-release (QTP-ER) formulations.. We hypothesized that QTP-IR is inferior to QTP-ER at any dose in efficacy for the acute treatment in schizophrenia and tested using a dose-response model-based network meta-analysis (NMA).. We searched PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov for randomized placebo-controlled trials comparing QTP-IR and/or QTP-ER for acute psychosis in patients with schizophrenia up to September 21, 2022. A random effect Bayesian dose-response model-based NMA was performed to compare the dose-response relationships between QTP-IR and QTP-ER.. The relationship between doses and antipsychotic effects was partially bell-shaped for QTP-IR but not for QTP-ER. The respective peak effect dose was 279.7 mg for QTP-IR and 557.2 mg for QTP-ER, with no significant difference in peak effect. QTP-IR ranging from 100 to 300 mg were significantly superior to QTP-ER at the same doses. In addition, QTP-IR ranging from 100 to 400 mg were significantly better than placebo, whereas QTP-ER ranging from 500 to 800 mg were significantly more effective than placebo. Moreover, QTP-IR 600 mg was significantly less effective than QTP-ER at the same dose. Furthermore, QTP-IR 700 mg was significantly superior to placebo, but significantly inferior to QTP-ER 600 mg.. QTP-IR may reach comparable peak responses and exhibit enhanced antipsychotic effects at lower doses than QTP-ER; the converse may be true at relatively high doses. Collectively, we propose a novel strategy to enhance the efficacy of QTP administration.

Topics: Antipsychotic Agents; Bayes Theorem; Delayed-Action Preparations; Humans; Network Meta-Analysis; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Aripiprazole is often prescribed to young people, although there remain unanswered questions about its effects on weight gain. This study undertook a meta-analysis of weight gain occurring in young people with early psychosis who were prescribed aripiprazole.. A systematic search was conducted for studies reporting on aripiprazole and weight change in young people with a psychotic disorder. A meta-analysis integrated the data into an estimate of effect size.. Eleven studies met the inclusion criteria amounting to 886 participants (mean age 18 years). The results showed significant weight gain averaging 2.7 kg. These increases were associated with a longer duration of exposure to aripiprazole but not a higher dosage.. The results highlight the importance of regular patient monitoring and the early implementation of interventions to manage antipsychotic-related weight gain.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Humans; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Weight Gain

Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP.. We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs).. Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94).. Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dementia; Humans; Network Meta-Analysis; Off-Label Use; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Withdrawal from psychoactive medication such as quetiapine is a well-documented phenomenon. Despite the extensive use of quetiapine, there have been few studies into the presence of discontinuation symptoms. We therefore performed a systematic review of published literature for evidence of quetiapine withdrawal or symptoms associated with discontinuation.. We searched PubMed, Embase, CINAHL, Medline, Web of Science, PsycINFO for articles containing the terms 'Quetiapine' AND 'withdraw. We included 13 papers, all of which were individual case reports. The quality of the individual case reports was sub-optimal, as assessed by the CARE Case Report Guidelines. There was an association between rapid cessation of quetiapine and onset of somatic symptoms such as nausea, vomiting, agitation, restlessness, diaphoresis, irritability, anxiety, dysphoria, sleep disturbance, insomnia, tachycardia, hypertension and dizziness. Three studies also reported the onset of a withdrawal dyskinesia characterised by abnormal choreiform movements as well as confusion and speech disturbance in some cases. However, these findings were limited by the number and quality of case reports identified.. Discontinuation symptoms are an uncommon side effect of quetiapine cessation, which may have clinical implications. Clinicians should therefore be alert to the possibility of quetiapine withdrawal in individuals who present with somatic symptoms or choreiform movements. However, large prospective studies are required to clarify this association.

Topics: Anxiety Disorders; Humans; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Substance Withdrawal Syndrome

This study aimed to compare the treatment effects of different antipsychotics for methamphetamine psychosis (MAP).. Clinical Trials, Cochrane Library, Pubmed, Scopus, and Web of Science were searched for short-term, randomized controlled trials (RCTs) from the inception to June 15, 2020. Standardized mean differences (SMDs) and odds ratios (ORs) were aggregated using random-effects pairwise comparisons and frequentist network meta-analyses (NMAs). Primary outcomes of interest were the main psychotic symptoms and dropout rates. We also rated the quality of NMA estimates.. This NMA included six RCTs of 395 patients with MAP. Six studied antipsychotics were aripiprazole, haloperidol, olanzapine, paliperidone extended-release, quetiapine, and risperidone. Risperidone is the most frequently studied antipsychotic, being investigated in four trials. Low quality of evidence was available to determine the efficacy of those antipsychotics for main psychotic symptoms. Aripiprazole was significantly inferior to olanzapine (SMD = 1.36, 95 % CI = 0.46-2.26), quetiapine (SMD = 1.13, 95 % CI = 0.28-1.98), haloperidol (SMD = 0.87, 95 % CI = 0.14-1.60), and paliperidone extended-release (SMD = 0.60, 95 % CI = 0.06-1.14). Olanzapine and quetiapine were superior to risperidone (SMD = -1.09, 95 % CI = -1.89 to -0.28 and SMD = -0.86, 95 % CI = -1.61 to -0.11, respectively). The dropout rates were not significantly different among the studied antipsychotics.. This analysis suggests that olanzapine or quetiapine may be a preferred antipsychotic for MAP, although the evidence for this was rated low-quality due to the high risk of bias or indirectness/intransitivity.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Haloperidol; Humans; Methamphetamine; Network Meta-Analysis; Olanzapine; Patient Dropouts; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Psychotic episodes in the postpartum period are life-threatening psychiatric emergencies, requiring urgent medical attention and admission to a psychiatric hospital.. Although the postpartum psychosis (PPP) is the most severe psychiatric disorder associated with parturition, there is little information about what interventions are most effective. Because there are no specific guidelines for the treatment of PPP, the aim of the present review was to examine the available evidence regarding the treatment of PPP.. The PubMed database was searched based on the title and the abstract, using the key words "postpartum psychosis," "postpartum psychosis antipsychotics," "postpartum psychosis treatment," and "postpartum psychosis pharmacotherapy," for both interventional and observational, irrespective of language.. A number of 14 publications met the study criteria, including case reports and case series. The antipsychotics (APs) use included both first generation APs, such as haloperidol and chlorpromazine, and second generation APs, mainly, olanzapine, quetiapine, and risperidone. The most frequently used AP was olanzapine. Olanzapine and quetiapine seem to be the most acceptable during breastfeeding. Proposed treatment algorithms for the successful management of PPP are discussed.. The existing studies to date do not allow to draw a definitive conclusion regarding which treatment is the most effective or the most adequate. Existing evidence suggests that APs alone or in combination are responsible for sustained remission and that treated PPP has a higher pace of improvement of the mental status, with a rapid discharge from the hospital. Clinical studies to compare the efficacy and safety of different APs in the PPP are needed to provide guidance on treatment interventions.

Topics: Antipsychotic Agents; Benzodiazepines; Female; Humans; Olanzapine; Postpartum Period; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Neuroleptic malignant syndrome (NMS) is a serious complication associated with the use of drugs that affect dopaminergic system neurotransmission. The occurrence of NMS during pregnancy or gestation is considered a life-threatening obstetric emergency.. We are reporting the first case in Latin America of NMS in one pregnant women with acute psychotic episode. One day after starting with antipsychotic therapy, she developed a fever higher than 39.0 °C with tachycardia, tachypnea, generalized muscle rigidity and somnolence, with creatine kinase (CPK) levels evidencing a result of 2800 U/L. She was treated successfully with levetiracetam, biperiden and quetiapine.. A search in PubMed, Embase and Ovid from 1988 to 2016 resulted in seven cases reported in either pregnant or puerperal women. In general, NMS resolves within 3-14 days; most NMS cases reported during pregnancy have involved the use of haloperidol (5 case reports) which is concordant with this report. The obstetric results were good in cases reported, only two women showed signs, among them: hyperemesis gravidarum and preterm delivery. Most of the pregnant women who had NMS presented other associated comorbidities, being mostly of infectious origin. In other investigations, it has been affirmed that NMS can become lethal in adults; however, in our search for pregnant women with this disease, no associated mortality was found.. NMS is seen infrequently during pregnancy. The clinical diagnosis requires high suspicion by the examiner. It is important that obstetricians timely recognize the condition.

Topics: Anticonvulsants; Antipsychotic Agents; Biperiden; Female; Humans; Levetiracetam; Neuroleptic Malignant Syndrome; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Young Adult

Antipsychotic drugs are the cornerstone of schizophrenia treatment and are also indicated for other psychotic and mood disorders. Different antipsychotic drugs and their formulations are available, though liquid forms have been overlooked.. Herein the added value of liquid antipsychotics is reviewed, with a focus on the recently introduced liquid quetiapine, a frequently used antipsychotic.. Liquid antipsychotics are easily administrated via the preferable oral route, while compliance under supervised administration is transparent. Liquid forms could be preferred in patients with swallowing difficulties, which are common in elderly patients and often concealed. In this population, the availability of liquid antipsychotics could prevent errors in medication administration, which could possibly render caregivers labile to any harm caused to the patient. Aspiration, however, remains a risk with liquid formulations. Common errors in medication administration are the omission of treatment and alteration of solid oral formulations. Regarding quetiapine, omission of treatment could be associated with non-adherence as well as discontinuation symptoms, while alteration of extended release formulation could alter its pharmacokinetics. Mildly agitated and cooperative patients are another target population of liquid antipsychotics, which can induce fast sedation avoiding involuntary intramuscular injections. The combination of sedative properties and low incidence of extrapyramidal symptoms makes liquid quetiapine a valuable option for these patients, yet the current evidence is limited.. The liquid form of quetiapine can facilitate pharmacotherapy of schizophrenia and can be defined as value added medicine bringing key benefits not only to the patients and caregivers but also to the health care system.

Topics: Antipsychotic Agents; Dosage Forms; Humans; Pharmaceutical Solutions; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.. Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.. A total of 17,615 unique records were identified, and seven RCTs (total N=241) met inclusion criteria. Five RCTs were placebo controlled, and two compared quetiapine against clozapine. The mean study duration was 12 weeks, and the mean daily quetiapine dose was 103 mg per day (range, 12.5-300 mg). In four of five placebo-controlled RCTs, quetiapine failed to demonstrate significant improvement of psychosis in parkinsonism compared with placebo. In two clozapine-comparator RCTs, quetiapine was better tolerated but no more effective than clozapine. Across all RCTs, the mean completion rates for quetiapine, clozapine, and placebo were 66%, 68.5%, and 66%, respectively. Quetiapine did not significantly worsen motor function.. The efficacy of quetiapine in RCTs for psychosis in parkinsonism is no better than that for placebo or clozapine. On the basis of novel data, clinicians should reevaluate traditional viewpoints on the benefits of quetiapine for psychosis in parkinsonism.

Topics: Antipsychotic Agents; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

Psychosis is a common problem for people treated for Parkinson's disease. The syndrome is quite stereotypic, with hallucinations being the most common, followed by delusions. While the hallucinations are usually not very bothersome, the delusions are typically paranoid in nature. Treatment is often, but not always, required.. This article reviews the therapeutic approaches of this syndrome focusing on drug treatments used once contributory factors have been removed. This includes a review of the evidence supporting the use of clozapine and, most recently, pimavanserin, the first drug with antipsychotic efficacy that has no effect on dopamine. Treatment with second generation antipsychotic drugs and cholinesterase inhibitors are also reviewed.. Clozapine and pimavanserin have proven efficacy for Parkinson's disease psychosis (PDP), without impairing motor function. In clozapine's favor are its antipsychotic benefits seen within 1 week and its effectiveness in improving tremor in PD. However, this is counterbalanced by the need for blood monitoring, despite the extremely low doses used, and sedation. Pimanvanserin is well tolerated, without sedation or other significant side effects. Its onset of benefit, however takes 4-6 weeks. While quetiapine is also frequently used, its efficacy is not supported by double blinded, randomized trials.

Topics: Antipsychotic Agents; Clozapine; Dopamine; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea

Aggressive, agitated or violent behaviour due to psychosis constitutes an emergency psychiatric treatment where fast-acting interventions are required. Risperidone is a widely accessible antipsychotic that can be used to manage psychosis-induced aggression or agitation.. To examine whether oral risperidone alone is an effective treatment for psychosis-induced aggression or agitation.. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (up to April 2017); this register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records into the register.. Randomised controlled trials (RCTs) comparing rapid use of risperidone and other drugs, combinations of drugs or placebo for people exhibiting aggression or agitation (or both) thought to be due to psychosis.. We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR) and for continuous data we calculated mean difference (MD), all with 95% confidence intervals (CI) and used a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce a 'Summary of findings' tables.. The review now contains data from nine trials (total n = 582) reporting on five comparisons. Due to risk of bias, small size of trials, indirectness of outcome measures and a paucity of investigated and reported 'pragmatic' outcomes, evidence was graded as very-low quality. None of the included studies provided useable data on our primary outcome 'tranquillisation or asleep' by 30 minutes, repeated need for tranquillisation or any economic outcomes. Data were available for our other main outcomes of agitation or aggression, needing restraint, and incidence of adverse effects.Risperidone versus haloperidol (up to 24 hours follow-up)For the outcome, specific behaviour - agitation, no clear difference was found between risperidone and haloperidol in terms of efficacy, measured as at least 50% reduction in the Positive and Negative Syndrome Scale - Psychotic Agitation Sub-score (PANSS-PAS) (RR 1.04, 95% CI 0.86 to 1.26; participants = 124; studies = 1; very low-quality evidence) and no effect was observed for need to use restraints (RR 2.00, 95% CI 0.43 to 9.21; participants = 28; studies = 1; very low-quality evidence). Incidence of adverse effects was similar between treatment groups (RR 0.94, 95% CI 0.54 to 1.66; participants = 124; studies = 1; very low-quality evidence).Risperidone versus olanzapineOne small trial (n = 29) reported useable data for the comparison risperidone versus olanzapine. No effect was observed for agitation measured as PANSS-PAS endpoint score at two hours (MD 2.50, 95% CI -2.46 to 7.46; very low-quality evidence); need to use restraints at four days (RR 1.43, 95% CI 0.39 to 5.28; very-low quality evidence); specific movement disorders measured as Behavioural Activity Rating Scale (BARS) endpoint score at four days (MD 0.20, 95% CI -0.43 to 0.83; very low-quality evidence).Risperidone versus quetiapineOne trial reported (n = 40) useable data for the comparison risperidone versus quetiapine. Aggression was measured using the Modified Overt Aggression Scale (MOAS) endpoint score at two weeks. A clear difference, favouring quetiapine was observed (MD 1.80, 95% CI 0.20 to 3.40; very-low quality evidence). No evidence of a difference between treatment groups could be observed for incidence of akathisia after 24 hours (RR 1.67, 95% CI 0.46 to 6.06; very low-quality evidence). Two participants allocated to risperidone and one allocated to quetiapine experienced myocardial ischaemia during the trial.Risperidone versus risperidone + oxcarba. Overall, results for the main outcomes show no real effect for risperidone. The only data available for use in this review are from nine under-sampled trials and the evidence available is of very low quality. This casts uncertainty on the role of risperidone in rapid tranquillisation for people with psychosis-induced aggression. High-quality pragmatic RCTs are feasible and are needed before clear recommendations can be drawn on the use of risperidone for psychosis-induced aggression or agitation.

Topics: Administration, Oral; Aggression; Antipsychotic Agents; Carbamazepine; Humans; Oxcarbazepine; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Tranquilizing Agents; Valproic Acid

To summarize and evaluate the existing literature regarding medications to treat Parkinson's disease (PD) psychosis.. MEDLINE (1946 to March 2017), EMBASE (1980 to March 2017), CINAHL (1982 to March 2017), and PsychInfo (1887 to March 2017) were searched using the following terms: Parkinson disease, Parkinson's disease, psychotic disorders, psychosis, delusions, and hallucinations.. The search was limited to randomized controlled trials (RCTs) reporting human outcomes. Data extracted included the following: study design, population, setting, intervention, control, outcomes related to psychosis and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool.. After assessment, 16 of 235 studies were included; 11 articles reported comparisons between active drug and placebo, whereas 5 compared clozapine and an active comparator. Placebo-controlled trials demonstrated benefit for clozapine (n = 2) and pimavanserin (n = 2), with no firm benefits observed for quetiapine (n = 4) or olanzapine (n = 3). Comparative studies demonstrated improved efficacy in symptom scores when clozapine or comparator agent (n = 2, quetiapine; n = 1, olanzapine; n = 1, risperidone; and n = 1, ziprasidone) was assessed alone. However, no comparator data suggest that one agent is better than another, and none are yet available for pimavanserin. Overall risk of bias across all studies was moderate to high.. Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Piperazines; Piperidines; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Urea

We performed a systematic review of randomized controlled trials to assess the high-level evidence regarding the role of quetiapine in the treatment of psychosis in patients with neurodegenerative parkinsonian disorders. Studies were included in the qualitative review if they (1) enrolled participants with diagnosis of Parkinson disease, Lewy body dementia, or any other neurodegenerative parkinsonian disorders; (2) assessed the efficacy of quetiapine; and (3) evaluated psychotic and motor outcomes using validated tools. Of the 341 manuscripts identified, 7 studies fulfilled our inclusion criteria. The studies' risk of bias was considered low. A total of 241 participants enrolled in these trials. Heterogeneity was high due to inclusion criteria, user definitions, assessment tools, and study design. Although not causing any motor deterioration, quetiapine failed to significantly reduce psychotic symptoms compared to placebo when objectively assessed on the Brief Psychotic Rating Scale, the most frequently reported scale in these studies. High loss to follow-up and dropout rates as well as significant improvement in psychotic symptoms in the placebo groups may have affected measurements of possible positive medication effects.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Lewy Body Disease; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Behavior Therapy; Benzodiazepines; Cognitive Behavioral Therapy; Dementia; Emotions; Humans; Hypotension, Orthostatic; Metabolic Syndrome; Neuroleptic Malignant Syndrome; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Psychosis in Parkinson's disease (PD) is one of the greatest determinants of nursing home placement and caregiver stress. Traditionally associated with medications with dopaminergic effect, it has now been linked to other medications and other stressors e.g. systemic illnesses. The development of hallucinations in a PD patient can herald the onset of dementia and usually predicts increased mortality risk. Medication reduction in PD psychosis usually reduces the symptoms; however, this comes at the cost of worsening motor function. If gradually decreasing the patient's medications does not resolve the psychosis, the treatment of choice is an atypical antipychotic. Though only clozapine has level A recommendation for this indication, other atypicals like quetiapine continue to get used for this purpose on account of the logistics involved with clozapine use. Cholinesterase inhibitors are also increasingly being used for PD psychosis on account of the association with dementia. The treatment of PD psychosis is an unmet need in PD management and search for suitable agents constitutes an active area of research in PD.

Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT

Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Humans; Molecular Targeted Therapy; Neurotransmitter Agents; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea

Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain; Clozapine; Dibenzocycloheptenes; Drug Therapy, Combination; Heterocyclic Compounds, 4 or More Rings; Humans; Impulsive Behavior; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Thiazoles; Violence

Parkinson's disease (PD) patients often develop psychotic symptoms that severely affect quality of life and limit the use of medications to ameliorate motor symptoms. Psychotic symptoms are a major cause for nursing home placement. While these symptoms do not always require treatment, they often do but antipsychotic drugs all share the common pharmacological mechanism of blocking dopamine D2 receptors which may worsen motor problems in this very vulnerable population. Double blind, placebo controlled trials (DBPCT) have shown that clozapine is effective at controlling the psychotic symptoms at doses far below those used in schizophrenia, without worsening motor function, even improving tremor. DBPCT have demonstrated that olanzapine worsens motor function without improving psychosis. Quetiapine has been shown in DBPCT to be free of motor side effects in PD patients but not effective, whereas many open label studies have indicated that quetiapine is effective. The other atypical have been the subjects of conflicting open label reports. The effects of the atypicals in PD psychosis is reviewed.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Women who are pregnant and who have a history of psychosis are commonly managed with antipsychotic medications. The evidence regarding the use of antipsychotics in pregnancy has been insufficient to provide adequate support for this practice and is a concern for clinicians and women alike. This review presents literature surrounding the use of antipsychotic medications in pregnancy, providing an overview of the historical and contemporary perspectives which influence clinicians prescribing practices. Data were sourced from Medline, CINAHL, PsycINFo, using the terms antipsychotics with pregnancy and psychosis or schizophrenia. This was expanded to include the most common atypical antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone and aripiprazole. Literature was found reporting the use of antipsychotic medications in pregnancy since the introduction of antipsychotics in the 1950s, comprising mainly of authors' reviews of the literature, case studies, retrospective reports, drug company registries and more recently a prospective comparative study. This review identifies that the literature provides no clear answer for clinicians as to the risk associated with the use of antipsychotics in pregnancy. To this effect, recently in Australia, the National Register of Antipsychotic Medications in Pregnancy was established to prospectively collect information regarding outcomes for mother and baby, when antipsychotic medications have been used during pregnancy.

Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes, Gestational; Dibenzothiazepines; Female; Humans; Infant, Newborn; Olanzapine; Piperazines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

Quetiapine is an atypical antipsychotic approved by the FDA (Food and Drug Administration) for use in the treatment of schizophrenia, acute mania, and bipolar depression. Pharmacologically, it has antagonistic effects on serotonin 5-HT1A and 5-HT2A, dopamine D1 and D2, histamine H1, and adrenergic alpha1 and alpha2 receptors. In addition to reports of its use in schizophrenia and bipolar disorder, many studies have examined the use of quetiapine in the treatment of anxiety disorders and substance use disorders. In the treatment of patients with psychotic or bipolar disorder with a comorbid substance abuse disorder even though quetiapine was prescribed primarily for the treatment of the underlying psychotic symptoms, patients taking this medication reported a significant reduction in substance use. Yet, there are also case reports of quetiapine abuse and dependence; in particular among prisoners and patients diagnosed with substance abuse. Though quetiapine should be used peroral, it is also used intranasally and intravenously in these patient groups. Moreover, in some cases quetiapine is combined with other substances, such as cocaine or marijuana, to increase sedation. This abuse of quetiapine is thought to occur due to the anxiolytic and sedative effects of the drug. There are no controlled studies on quetiapine dependence in the literature and it remains unknown whether or not quetiapine causes dependence. This review aimed to present all published case reports on quetiapine abuse and to discuss the possible mechanisms that underlie its abuse and dependence.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published.. The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD.. A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.. Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years.. Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts.

Topics: Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Comorbidity; Delusions; Dementia; Depression; Dibenzothiazepines; Disease Progression; Guidelines as Topic; Hallucinations; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report; Risperidone

This 10-day, single-center, open-label, randomized, crossover study compared pharmacokinetic profiles and tolerability of extended release quetiapine fumarate (quetiapine XR) with quetiapine immediate release (quetiapine IR) in patients with schizophrenia, schizoaffective disorder or bipolar disorder. After a 2-day lead-in period during which patients received quetiapine XR 300 mg once daily, patients were randomized to quetiapine IR 150 mg twice daily followed by quetiapine XR 300 mg once daily, or quetiapine XR 300 mg once daily followed by quetiapine IR 150 mg twice daily. Pharmacokinetic parameters were evaluated at the end of each 4-day treatment period at steady state. Vital signs, laboratory values, and adverse events (AEs) were recorded throughout the study. The least squares means (90% confidence interval) of the ratio of the area under the plasma concentration-time curve over a 24 h dosing interval (AUC ([0-24 h])) for quetiapine XR/IR was 1.04 (0.92-1.19) and within the pre-defined range set for equivalence (0.80-1.25). Maximum plasma concentration at steady state (C(max)) was approximately 13% lower for quetiapine XR than for quetiapine IR (495.3 versus 568.1 ng/mL), time to reach C(max) (t(max)) was 5 h versus 2 h and mean concentration at the end of 24 h dosing interval (C(min)) was 95.3 versus 96.5 ng/mL, respectively. No patients withdrew from the study owing to AEs and there were no serious AEs or deaths related to study medication. No unexpected AEs, changes in vital signs or laboratory values were observed. These findings suggest that modifying the formulation does not change the overall absorption or elimination of quetiapine, and support emerging clinical evidence for the use of quetiapine XR as a once daily treatment in patients initiating therapy or those established on quetiapine IR.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Cross-Over Studies; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

Akathisa is one of the most common and distressing neuroleptic-induced extrapyramidal side effects. Although it is well recognized in the context of conventional antipsychotic medications, there have been recent concerns raised by clinicians and researchers that this syndrome is overlooked in relation to second-generation or atypical antipsychotics. This review examines the recent literature relevant to second-generation antipsychotic (SGA)-induced akathisia.. Recent studies using large databases clearly indicate that extrapyramidal side effects, in particular akathisia, do occur with the SGAs, although the frequency is not as high as with the conventional antipsychotics. Risk factors include use of high doses, high potency SGAs, or combinations of SGAs with other psychotropic drugs, bipolar depression, palliative care settings, and comorbid substance abuse in psychosis. The dopamine hypothesis remains plausible for understanding the pathophysiology of akathisia. There is emerging evidence that mirtazapine may be useful in the treatment of acute akathisia.. Even though akathisia is less prevalent with SGAs than with the first-generation drugs, it remains clinically important and all clinicians should be conversant with its recognition and management.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Isoxazoles; Olanzapine; Piperazines; Piperidines; Prevalence; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Sulpiride; Thiazoles

Topics: Acute Disease; Adult; Affect; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Evidence-Based Medicine; Hospitalization; Humans; Male; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Treatment Outcome; Valproic Acid

The management of patients with first-episode psychosis (FEP) is a difficult, but challenging task. Early and efficient treatment may influence long-term clinical outcome. Atypical antipsychotics (A-AP) are commonly prescribed in this population, but few data exist to establish their appropriate usage in the management of FEP. Our purpose is to review the literature and to summarize current data on the prescription of A-AP in FEP.. Studies assessing efficacy or safety of A-AP in FEP were identified by searches in Medline (up to April 2006). The following nine drugs were considered for this review: clozapine, olanzapine, risperidone, amisulpride, aripiprazole, quetiapine, ziprasidone, zotepine, and sertindole.. Only four A-AP (clozapine, quetiapine, olanzapine, and risperidone) were evaluated as treatment of FEP. All of them show the same efficacy as conventional antipsychotics (C-AP). Clozapine has no benefit over C-AP in the treatment of naive patients. It entails a high rate of treatment discontinuation because of the need for regular white blood cell monitoring explained by the risk of agranulocytosis. Hence, clozapine may not be a first-line treatment of FEP. Tolerance to quetiapine and olanzapine is better than C-AP regarding extrapyramidal side effects, but weight gain induced by these two A-AP may be very disabling in a young population. Considering results from head-to-head comparative studies, olanzapine may be more effective than risperidone when an affective component is associated with the FEP symptomatology, but more data are needed to demonstrate this point. Risperidone is a relatively well-tolerated compound when it is prescribed at doses lower than 4 mg/d. It is the only A-AP that showed greater efficacy than C-AP to prevent relapse in patients with FEP. Unfortunately, information regarding the preventive efficacy of the other A-AP are lacking.. Further studies, particularly longer-term studies, are needed to explore the impact of A-AP prescription in FEP on the course of psychotic disorders. The common use of A-AP as treatment of FEP is justified by a relatively better tolerance compared to C-AP, and by the hypothesis-not demonstrated-of a better effect on long-term outcome.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index

Psychosis due to dopamimetic treatment is a difficult problem in patients with Parkinson's disease (PD). The aim of this structured review with meta-analysis was to evaluate which neuroleptic drugs can efficiently be used to treat drug-induced psychosis (DIP) in Parkinson's disease. Electronic databases were screened for the key words Parkinson's disease and psychosis. Only 7 trials with a satisfactory allocation concealment and data reporting were included into the study. Two trials compared low-dose clozapine versus placebo with a significantly better outcome for clozapine regarding efficacy and motor functioning. In one trial clozapine was compared against quetiapine showing equivalent efficacy and tolerability. However, in two placebo controlled trials quetiapine failed to show efficacy. In two further placebo controlled trials olanzapine did not improve psychotic symptoms and significantly caused more extrapyramidal side effects. Based on randomized trial-derived evidence which is currently available, only clozapine can be fully recommended for the treatment of DIP in PD. Olanzapine should not be used in this indication.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Data Interpretation, Statistical; Dibenzothiazepines; Dopamine; Dopamine Agents; Humans; Olanzapine; Parkinson Disease; Psychotic Disorders; Quality Assurance, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Aripiprazole; Cholinesterase Inhibitors; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Male; Parkinson Disease; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones

Atypical antipsychotics offer broader efficacy and improved tolerability compared with conventional agents. Many patients currently treated with conventional antipsychotics continue to experience persistent symptoms or troublesome side effects and may benefit from a change to one of the newer atypical agents. There are also significant differences in the side-effect profiles of the atypicals, such that a switch from one atypical agent to another could offer advantages to many patients. Unfortunately, many clinicians remain uncertain about the switching process and are reluctant to initiate change. The aim of this review is to identify the indications for a switch in antipsychotic therapy with a focus on recent switching data for the atypical antipsychotic, quetiapine. The clinical aspects of quetiapine's receptor binding characteristics are reviewed including the implications of the low D(2) antagonist properties that make quetiapine the treatment of choice when EPS persists with other atypical antipsychotics. Practical guidelines are given for managing the process of changeover, for avoiding pitfalls and for maximizing the chances of a successful switch. For example, when managing the antipsychotic crossover, it is important to consider the psychological effects of switching arising from symptom and side-effect changes. Finally, advice is provided on the assessments necessary when evaluating the success of a change in therapy, together with guidance on the optimal duration of treatment trials.

Topics: Animals; Antipsychotic Agents; Depressive Disorder; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Psychotic Disorders; Quetiapine Fumarate

Aggression, agitation or psychosis occur in the majority of people with dementia at some point in the illness. There have been a number of trials of atypical antipsychotics to treat these symptoms over the last five years, and a systematic review is needed to evaluate the evidence in a balanced way.. To determine whether evidence supports the use of atypical antipsychotics for the treatment of aggression, agitation and psychosis in people with Alzheimer's disease.. The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 December 2004 using the terms olanzapine, quetiapine, risperidone, clozapine, amisulpride, sertindole, zotepine, aripiprazole, ziprasidone. This Register contains articles from all major healthcare databases and many ongoing trials databases and is updated regularly.. Randomised, placebo-controlled trials, with concealed allocation, where dementia and psychosis and/or aggression were assessed.. 1. Two reviewers extracted data from included trials2. Data were pooled where possible, and analysed using appropriate statistical methods3. Analysis included patients treated with an atypical antipsychotic, compared with placebo. Sixteen placebo controlled trials have been completed with atypical antipsychotics although only nine had sufficient data to contribute to a meta-analysis and only five have been published in full in peer reviewed journals. No trials of amisulpiride, sertindole or zotepine were identified which met the criteria for inclusion. The included trials led to the following results:1. There was a significant improvement in aggression with risperidone and olanzapine treatment compared to placebo.2. There was a significant improvement in psychosis amongst risperidone treated patients.3. Risperidone and olanzpaine treated patients had a significantly higher incidence of serious adverse cerebrovascular events (including stroke), extra-pyramidal side effects and other important adverse outcomes.4. There was a significant increase in drop-outs in risperidone (2 mg) and olanzapine (5-10 mg) treated patients.5. The data were insufficient to examine impact upon cognitive function.. Evidence suggests that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extra-pyramidal symptoms. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is marked risk or severe distress. Although insufficient data were available from the considered trials, a meta-analysis of seventeen placebo controlled trials of atypical neuroleptics for the treatment of behavioural symptoms in people with dementia conducted by the Food and Drug Administration (using data not in the public domain) suggested a significant increase in mortality (OR 1.7).

Topics: Aggression; Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone

To review practical evidence-based treatment of behavioural symptoms in dementia. SOURCES OF INFORMATION MEDLINE: Was searched from January 1966 to December 2004 and PsycINFO from January 1967 to December 2004 using the key words "BPSD" (behavioural and psychological symptoms of dementia) and "behavioral disturbances dementia." I also reviewed the bibliographies of recent review papers and original articles.. Family physicians who manage hospital inpatients and care for people in nursing homes are asked to prescribe medications for demented patients. This review discusses alternatives to drugs, indications for appropriate use of drugs, frequently encountered side effects of drugs, and considerations for those with neuroleptic sensitivity. I suggest an approach that employs a combination of behavioural, environmental, and pharmacologic interventions to address disruptive behaviour in patients with dementia.. Optimal treatment of behavioural disturbances in patients with dementia involves nonpharmacologic approaches and using medications with demonstrated efficacy. Pharmacologic treatment should target only those symptoms or behaviours that respond to medication. This approach minimizes unnecessary medication use and reduces adverse outcomes.

Topics: Aged; Antipsychotic Agents; Behavior Therapy; Dementia; Dibenzothiazepines; Environment; Humans; Male; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate

Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications.. Selective review of endocrine and metabolic effects of psychotropic medications in pediatric populations, with a focus on monitoring and management strategies.. Because youth are still developing at the time of psychotropic drug exposure, most reference values need to be adjusted for gender and age. As in adults, youngsters receiving lithium require monitoring for thyroid dysfunction. Psychostimulants appear to cause mild reversible growth retardation in some patients, most likely because of decreased weight or slowing of expected weight gain; some patients may experience clinically significant reductions in adult height. Although still controversial, valproate use has been associated with an increased risk for polycystic ovary syndrome, in addition to causing weight gain. Although more data are required, children and adolescents appear to be at higher risk than adults for antipsychotic-induced hyperprolactinemia, weight gain, and possibly, associated metabolic abnormalities, which is of particular concern.. Clinicians and caregivers need to be aware of potential endocrine and metabolic adverse effects of psychiatric medications. A careful selection of patients, choice of agents with potentially lesser risk for these adverse events, healthy lifestyle counseling, as well as close health monitoring are warranted to maximize effectiveness and safety.

Topics: Adolescent; Antipsychotic Agents; Child; Dibenzothiazepines; Drug Administration Schedule; Endocrine System Diseases; Female; Humans; Hyperprolactinemia; Life Style; Lithium Compounds; Male; Metabolic Diseases; Polycystic Ovary Syndrome; Psychotic Disorders; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Valproic Acid; Weight Gain

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Infant, Newborn; Infanticide; Pregnancy; Pregnancy Complications; Psychotic Disorders; Puerperal Disorders; Quetiapine Fumarate; Risk Assessment; Risk Factors; Schizophrenia; Schizophrenic Psychology; Secondary Prevention; Social Support

Thirty years ago, psychiatrists had only a few choices of old neuroleptics available to them, currently defined as conventional or typical antipsychotics, as a result schizophrenics had to suffer the severe extra pyramidal side effects. Nowadays, new treatments are more ambitious, aiming not only to improve psychotic symptoms, but also quality of life and social reinsertion. Our objective is to briefly but critically review the advances in the treatment of schizophrenia with antipsychotics in the past 30 years. We conclude that conventional antipsychotics still have a place when just the cost of treatment, a key factor in poor regions, is considered. The atypical antipsychotic drugs are a class of agents that have become the most widely used to treat a variety of psychoses because of their superiority with regard to extra pyramidal symptoms. We can envisage different therapeutic strategies in the future, each uniquely targeting a different dimension of schizophrenia, be it positive, negative, cognitive or affective symptoms.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptors, Dopamine; Receptors, Serotonin; Risperidone; Schizophrenia; Thiazoles

The authors presents the state of knowledge on the prevalence and proposed mechanisms leading to weight gain during treatment with atypical antipsychotics. A short review on the therapeutic approaches is also supplied.

Topics: Antipsychotic Agents; Body Weight; Clozapine; Dibenzothiazepines; Humans; Hyperlipidemias; Leptin; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles; Weight Gain

The first compounds showing efficacy in the treatment of schizophrenia and other psychotic disorders was chlorpromazine, an anti-histaminic compound casually observed to possess antipsychotic effects. The discovery of the real mechanism of action of antipsychotic substances dates back to the 1960s, when researchers found that these compounds act as dopamine receptor antagonists. Unfortunately, this type of drugs cannot block the D2 receptors only in the mesolimbic dopaminergic pathway (which mediates their therapeutic effects), because of their non-selective D2 receptor blockage in both the mesolimbic and striatal regions, and the consequent appearance of side effects related to striatal interaction in the same dosage range as is needed for the therapeutical effects. Clozapine, discovered in the early 1970s, seemed to represent the solution to contrast these side effects, as it possesses antipsychotic activity without inducing extrapyramidal disorders in humans or catalepsy in rats; for this reason, it was defined as an "atypical" antipsychotic drug. Later, other beneficial properties, such as improvement of negative symptoms and of cognitive dysfunction and efficacy in neuroleptic-resistant schizophrenia, were included in the definition of "atypical". In recent years, the appearance of new atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone) has opened new ways to therapy. The aim of this paper is to review literature about newer antipsychotics, focusing on their advantages in terms of efficacy and side effect profiles when compared to classical and older atypical antipsychotics, and to evaluate the efficacy of the different new antipsychotics when compared to one another.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Cognition; Dibenzothiazepines; Drug Interactions; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Tardive dyskinesia is a chronic drug-induced movement disorder that tends to be persistent in older adults who are treated with antipsychotics. Tardive dyskinesia can affect older patients both physically and psychologically, leading to frequent falls, difficulty eating, and depression. While atypical antipsychotics may cause tardive dyskinesia, the percentage is usually significantly lower than with conventional antipsychotics. Using atypical antipsychotics, particularly at lower doses, may aid in preventing symptoms of tardive dyskinesia in older adults.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Humans; Incidence; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative disorder now considered to be the second most common cause of dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls, nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially fatal complication of neuroleptic sensitivity, which affects approximately 50% of DLB patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB. Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Serotonin Antagonists; Thiazoles; Treatment Outcome; United States

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of Parkinson's disease (PD) patients and are the single most important precipitant for nursing home placement, which carries a grave prognosis. In addition, parkinsonism is a frequent accompaniment to the more common dementing syndromes, Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB). The five most recent antipsychotic drugs approved by the Food and Drug Administration in the United States have been marketed as "atypical" antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms when used in schizophrenia patients. The use of these newer antipsychotic drugs in PD and other parkinson-sensitive populations represents the most stringent test to their freedom from motor side effects. To date, clozapine, risperidone, olanzapine, and quetiapine have been studied in parkinson-vulnerable populations. This article reviews the data and highlights the differences that these four drugs have on motor function. It also emphasizes the challenges in evaluating the available data on the motor effects of AA, especially on the non-PD elderly and cognitively impaired population. Suggestions are made for future research to improve the interpretability of these studies.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia, Vascular; Dibenzothiazepines; Hallucinations; Humans; Iatrogenic Disease; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

During 20th century serious mental disorders were divided into two groups according symptomatology and course of disorder. Individuals with dominating disturbance of perception, thinking and cognition were basically diagnosed having schizophrenic. Individuals with mood disturbance were basically diagnosed having affective disorders. However, there were patients who did not fit neatly into either category. In 1933 Jocob Kasanin introduced the term "schizoaffective psychosis". Scientific discussions involved the possibility that schizoaffective disorder was conceptualized most accurately as following: a type of schizophrenia, a type of affective disorder, a unique disorder that was separate from both schizophrenia and bipolar disorder, an arbitrary categorization of clinical symptoms that marked a continuum between schizophrenia and affective illness, a heterogeneous collection of "interforms" between schizophrenia and affective disorders. However, diagnosis of schizoaffective disorder is included both in DSM-IV-TR and ICD-10. Schizoaffective disorder is listed in the category "schizophrenia and other psychotic disorders". The differential diagnosis includes basically either schizophrenia or affective disorder. The epidemiological status of schizoaffective disorder is somewhat uncertain compared with schizophrenia because of dilemmas related to diagnosis and classification of the disorder. Treatment of schizoaffective disorder comprises psychotropic medication, supportive psychotherapy, social care, rehabilitation. The most important groups of psychotropic medications are: antipsychotics, antidepressants and mood stabilizers. Atypical antipsychotics are the first-line medication for schizoaffective disorder due to their pharmacological properties. In the case of schizoaffective disorders combination of atypical antipsychotics with antidepressants seems to be useful. Novel antidepressants have priority for the combination mentioned above. Peculiarities of mechanism of action of antidepressant are important for combinations. Mood stabilizers seem to be useful for treatment of certain type of schizoaffective disorder as well.

Topics: Adolescent; Amisulpride; Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Carbamazepine; Child; Diagnosis, Differential; Dibenzothiazepines; Dogs; Female; Humans; Imidazoles; Indoles; Lithium Carbonate; Male; Mianserin; Middle Aged; Mirtazapine; Olanzapine; Piperazines; Pirenzepine; Placebos; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Sulpiride; Thiazoles; Time Factors

Quetiapine is a novel dibenzothiazepine atypical antipsychotic. Quetiapine shows affinity for various neurotransmitter receptors including serotonin, dopamine, histamine, and adrenergic receptors and has binding characteristics at the dopamine-2 receptor similar to those of clozapine. In animal models, the drug has a preclinical profile suggestive of antipsychotic activity with a reduced tendency to cause extrapyramidal symptoms (EPS) and sustained prolactin elevation. For example, quetiapine alters neurotensin neurotransmission and c-fos expression in limbic but not motor brain regions. The drug also demonstrates clozapine-like activity in a range of behavioral and biochemical tests and may possess neuroprotective properties. In humans, quetiapine exhibits linear pharmacokinetics with a mean terminal half-life of 7 hours. The primary route of elimination of quetiapine is through hepatic metabolism. Although not affected by smoking, alterations in quetiapine disposition due to age or hepatic impairment are manageable by appropriate dosage reduction. The optimal dosing range for quetiapine is 150 to 750 mg/day, and recent results suggest that once-daily dosing may be suitable for some patients. Finally, imaging studies with positron emission tomography confirm significant differences between quetiapine and typical antipsychotics that may be indicative of their differences in mechanism of action and propensity for producing EPS.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Gene Expression; Genes, Immediate-Early; Humans; In Vitro Techniques; Psychotic Disorders; Quetiapine Fumarate; Receptors, Neurotransmitter; Tomography, Emission-Computed

Behavioral problems associated with psychosis in the elderly have a significant negative impact on patients' quality of life and can lead to placement in a nursing home. Because of their decreased propensity to produce extrapyramidal symptoms, atypical antipsychotics such as quetiapine hold promise in the treatment of these vulnerable patients. Quetiapine may, in theory, be particularly advantageous in this regard because of its lack of anticholinergic activity and its relatively loose binding to dopamine receptors. This article reviews the somewhat limited number of clinical studies of the use of quetiapine in treating older patients with schizophrenia and other psychotic disorders, patients with psychosis associated with Alzheimer's disease or dementia with Lewy bodies, and patients with Parkinson's disease and drug-induced psychosis.

Topics: Age Factors; Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dementia; Dibenzothiazepines; Double-Blind Method; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Treatment Outcome

The atypical antipsychotic quetiapine has been examined in children and adolescents in a randomized clinical trial, a number of open-label studies, and several chart review studies. Although only a small amount of information exists, most studies indicate that quetiapine is effective and well tolerated in various pediatric populations. Because quetiapine appears to be well tolerated in the young and associated with manifest salutary effects, it seems to be a promising agent that has potential for use in children and adolescents. This article reviews studies of quetiapine in the treatment of children and adolescents with a variety of psychiatric disorders. Despite these encouraging findings, the number of studies is small, and some have methodological limitations. Methodologically rigorous studies with substantive numbers of subjects are needed to confirm or refute these preliminary impressions.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Autistic Disorder; Basal Ganglia Diseases; Child; Clinical Trials as Topic; Dibenzothiazepines; Humans; Medical Records; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome

The use of control placebos in clinical trials of new antipsychotic medications is increasingly under examination. The active controlled equivalence study could offer a potential alternative design. First, however, it must be clear that any proposed standard control agent has been consistently superior to placebo in previous studies.. Through a Freedom of Information Act request, we identified nine placebo-controlled trials of risperidone, olanzapine, or quetiapine.. Meta-analysis indicated that the pooled estimate of the true population effect size +/- SE was 0.46 +/- 0.06 for categorical response rates and >0.53 +/- 0.07 for the continuous Brief Psychiatric Rating Scale change score outcome measure. If the desired detectable effect size is set very conservatively at a 95% confidence lower bound for the estimate of true effect size, statistical power for random samples of 80 per group drawn from a population of subjects similar to that of the nine meta-analyzed studies is.67 for categorical response rates and >.82 for the continuous measure, based on one-sided alpha =.05.. These data suggest substantial confidence that a therapeutic dose of an atypical antipsychotic will be statistically superior to placebo in an adequately sized randomized trial, when reporting a continuous measure as the principal outcome.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone

In general, antipsychotic agents have diverse actions on a wide range of neurotransmitter systems. Data strongly suggest that a number of these systems may play a role in the regulation of body weight. In addition to having very distinct pharmacologic profiles, individual agents possess discrete weight gain liabilities. This article briefly reviews the evidence for the involvement of specific neurotransmitter systems in the control of body weight and describes the relevant pharmacologic characteristics of individual antipsychotic agents. By comparing the pharmacologic profiles of specific antipsychotic agents with their respective weight gain liabilities, this article attempts to gain an insight into the specific receptors underlying a drug's propensity to induce weight gain. However, there is still much to be learned concerning weight control mechanisms, and the role of many of the receptors at which antipsychotic agents are active remains unclear. In spite of this, an overview of current knowledge in the field may facilitate prediction of a potential novel antipsychotic agent's weight gain liability.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Eating; Humans; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Rats; Receptors, Neurotransmitter; Schizophrenia; Thiazoles; Weight Gain

The newest atypical antipsychotic medication to be approved by the U.S. Food and Drug Administration, quetiapine is a drug that awaits a wide range of clinical and head-to-head comparisons. Nevertheless, clinical trials currently available suggest that quetiapine has a beneficial side effect profile, particularly with regard,to extrapyramidal symptoms. To date, quetiapine has also proved effective in the treatment of schizophrenia, but its efficacy, while clearly superior to that of placebo, seems no greater than that of haloperidol or chlorpromazine. Clinical trials have supported the use of quetiapine in treating elderly patients. Further research is necessary to establish the clinical profile of quetiapine.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Dibenzothiazepines; Humans; Placebos; Psychotic Disorders; Quetiapine Fumarate; Receptors, Adrenergic, alpha; Receptors, Dopamine; Receptors, Neurotransmitter; Receptors, Serotonin; Schizophrenia; Weight Gain

Atypical neuroleptic agents are an excellent, safer, and more effective alternative to the widespread practice of maintenance adjunctive treatment with traditional neuroleptic agents in patients with bipolar disorder. Currently, a number of prospective studies are available with clozapine, risperidone, olanzapine, and quetiapine in the treatment of bipolar disorder. Most are short-term studies, although longer-term data are becoming available. Four double-blind studies of acute mania have been conducted with risperidone and olanzapine, leading to recent Food and Drug Administration approval for olanzapine in the indication of acute mania. Given the limited longer-term data, and the evidence for mostly adjunctive benefits with these agents, it seems unlikely that these agents will prove to be primary mood stabilizers in their own right. Nonetheless, they serve an important role as adjunctive treatments along with standard mood stabilizers in the rational polypharmacy of bipolar disorder. To date, differences in efficacy have not been established. However, differences in the side effect of weight gain may be even more relevant in bipolar disorder than in schizophrenia due to the need to use standard mood stabilizers that often potentiate such weight gain.

Topics: Acute Disease; Algorithms; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome; Valproic Acid

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Aggressive behavior of psychotic patients impacts all aspects of their clinical care. Better treatments to address this problem are needed, and atypical antipsychotics, such as clozapine, risperidone, and perhaps quetiapine, have shown promise. However, studying the psychopharmacology of aggression is difficult because of the many methodological problems that arise in the design of appropriate clinical trials. These include imprecise definitions of aggression, the difficulty of measuring outcome because of the relative rarity of aggressive events, bias in the selection of patients for study, inadequate and inappropriate control groups, and inattention to comorbidities and concomitant medications in analyzing results. Since the usual outcome measure is the aggressive event rate, a large sample size and lengthy baseline and trial periods are required when this rate is low. Furthermore, formidable practical and ethical obstacles interfere with the many sound techniques (e.g. randomization) used in typical designs of psychopharmacological clinical trials. Current research methods should be modified and new ones developed in order to progress in assessing the antiaggressive effects of treatments.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Disease Progression; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Research Design; Risperidone

Soon after the introduction of antipsychotic drugs into clinical practice, these agents were observed to be capable of producing not only acute extrapyramidal ("parkinsonian") side effects, but also later occurring abnormal involuntary movements that came to be called tardive dyskinesia. Since antipsychotic drugs are used in a variety of conditions that include psychotic features, studies have attempted to determine whether specific diagnostic subgroups may experience different degrees of vulnerability to drug-induced movement disorders. This issue is important not only to inform clinical practice, but also to provide clues to pathophysiology. A number of studies suggest that patients with affective disorders are at greater risk for developing tardive dyskinesia (controlling, to the extent possible, for other relevant variables such as age, sex, length of treatment). Encouraging preliminary data with new antipsychotic drugs such as olanzapine suggest that the risk of tardive dyskinesia associated with long-term antipsychotic drug use may be substantially reduced. This would go a long way toward improving the benefit-to-risk ratio of antipsychotic drug treatment, particularly in patients with affective disorders.

Topics: Adult; Affective Disorders, Psychotic; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Imidazoles; Indoles; Male; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Psychotic symptoms have become increasingly common in patients with idiopathic Parkinson's disease and other parkinsonian syndromes. This increased prevalence of psychoses is in part a reflection of the greater longevity of people with Parkinson's disease and, to a certain extent, is a consequence of our success in treating the motor symptoms of these syndromes. The psychotic symptoms associated with Parkinson's disease can be as varied as the motor symptoms. They stem from interactions between the underlying neuropathologies of the syndromes and the adverse effects associated with chronic antiparkinsonian drug administration. In patients with advanced Parkinson's disease, there is also a high prevalence of affective comorbidity. This increase in affective symptoms and the relatively high incidence of cognitive and affective side effects of the antiparkinsonian medications contribute to the increase in psychoses observed in these older patients. The most significant risk factors for developing psychosis in Parkinson's disease are (1) coexistence of dementia, (2) protracted sleep disturbances, and (3) nighttime use of long-acting dopaminomimetics. This article reviews the phenomenology, pathophysiology, and treatment of psychosis associated with parkinsonism and discusses how atypical antipsychotic medications have revolutionized the management of the symptoms and improved the quality of life of those affected.

Topics: Algorithms; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Comorbidity; Decision Trees; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate

Clinical studies with clozapine have clearly demonstrated its superior efficacy over that of conventional antipsychotics in treatment-resistant schizophrenic patients. In comparative trials with these drugs, considerably more patients respond to treatment with clozapine than to conventional antipsychotic medication. Recently, new antipsychotics, such as olanzapine, quetiapine, risperidone, sertindole, and zotepine, have been introduced, but extensive data on their effects in treatment-resistant patients are not yet available. Published studies have drawn criticism in terms of inappropriate titration schedules, nonequivalent dosing between treatment groups, short treatment duration, and inadequate sample sizes. Further research will be needed to determine whether novel antipsychotics may substitute for clozapine in the future or whether clozapine will retain its unique role in the management of patients suffering from difficult-to-treat schizophrenic disorders.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Double-Blind Method; Drug Resistance; Humans; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Since the discovery of the neuroleptics in 1952, french psychiatrists have proposed a classification of neuroleptics taking into account the pharmalogical and therapeutic differences between these drugs. They distinguished three different clinical effects of neuroleptics: sedative effects, effects on the positive symptoms of schizophrenia and effects on the negative symptoms. However these agents have many side effects including the extrapyramidal syndrome (EPS), akathisia, dystonia and parkinsonism. These side effects occur in up to 75% of patients receiving typical neuroleptics and are the main cause of non-compliance. Since the eighties, clozapine was introduced for use in refractory patients because it has a better efficacy (than haloperidol) specifically on negative symptoms, a better tolerance and fewer effects. After clozapine, several new antipsychotic agents are now available, such as risperidone, olanzapine, sertindole, quietapine, ziprasidone ... Their therapeutical effects are probably linked with a dual antagonist effect on 5HT2 and D2 receptors. The present article reviews the evolution of the use of these new agents, their real efficacy, their adverse effects and their expanding indications. Future research will more clearly establish appropriate treatment guidelines for their use. These new antipsychotics should add a positive modification in schizophrenia care and in some mood disorders. The approach consisting on individualizing dimensions and clusters analysis might be useful to test the efficiency of each antipsychotic on a syndromic dimension.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles

While approximately 70% of patients with schizophrenia and other psychotic disorders show a clear-cut reduction of symptoms in clinical trials, there is considerable variation in individual patient outcome, ranging from complete remission to absolute refractoriness. When additional indicators of treatment outcome are considered, such as cognitive and occupational and social functioning, it is clear that the overall outcome for schizophrenia is far from satisfactory. For many schizophrenic patients, treatment with conventional antipsychotic agents is not fully effective, and one approach has been to increase the administered dose. However, raising the dose increases the likelihood of side effects and may significantly compromise patient compliance. The availability of atypical antipsychotic agents represents a significant step forward for those patients who are nonresponsive to conventional antipsychotics, offering proven efficacy, a lower risk of extrapyramidal symptoms, and improved clinical outcomes.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and parkinsonism--associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance Withdrawal Syndrome

Topics: Antipsychotic Agents; Benzodiazepines; Benzothiazoles; Clinical Trials as Topic; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Pramipexole; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles

To evaluate 1) whether early nonresponse to antipsychotics predicts nonresponse and nonremission, 2) patient and illness characteristics as outcome predictors, and 3) response prediction of 30-item Positive and Negative Syndrome Scale (PANSS-30) compared with 6-item PANSS (PANSS-6) and Clinical Global Impressions-Improvement Scale (CGI-I) in youths with first-episode psychosis.. Post hoc analysis from a 12-week, double-blinded, randomized trial of aripiprazole vs extended-release quetiapine in adolescents (age 12-17 years) with first-episode psychosis was performed. Early nonresponse (week 2 or week 4) was defined as <20% symptom reduction (PANSS-30) (or <20% symptom reduction [PANSS-6] or CGI-I score 4-7 [less than "minimally improved"]). Nonresponse (week 12) was defined as <50% symptom reduction (PANSS-30). Nonremission (week 12) was defined as a score of >3 on 8 selected PANSS-items. Positive/negative predictive values (PPV/NPV) and receiver operating characteristics, binary logistic regression models, and PPV/NPV using PANSS-6 and CGI-I were analyzed.. Of 113 randomized patients, 84 were included in post hoc analysis (mean [SD] age = 15.7 [1.3] years; 28.6% male). The 12-week symptom decrease was 31.9% [27.9%], most pronounced within the first 2 weeks (61.1% of total PANSS reduction). Response (27.4%) and remission (22.6%) rates were low. Results indicated that early nonresponse reliably predicted 12-week nonresponse (PPV: week 2, 82.2%; week 4, 90.0%) and nonremission (PPV: week 2, 80.0%; week 4, 90.0%); early nonresponse at week 4 was a statistically significant baseline predictor for 12-week nonresponse; and PANSS-6 had similar predictive significance as PANSS-30. However, outcomes were heterogeneous using CGI-I.. In youths with first-episode psychosis showing early nonresponse to aripiprazole or extended-release quetiapine, switching antipsychotic drug should be considered. PANSS-6 is a feasible and clinically relevant alternative to PANSS-30 to predict 12-week nonresponse/nonremission.. Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis; https://www.. gov/; NCT01119014.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Double-Blind Method; Female; Humans; Male; Predictive Value of Tests; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.. From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.. The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea.. Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Female; Follow-Up Studies; Haloperidol; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Young Adult

Patients with schizophrenia and comorbid alcohol use disorder remain understudied. This post hoc analysis evaluated data from Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia study (January 2001-December 2004).. Patients without substance abuse (except marijuana use) in the month before study entry were categorized into those with a history of alcohol use disorder (SZ + AUD) within 5 years before study entry and those without alcohol use disorder (SZ-only) per DSM-IV criteria. Time to first and recurrent exacerbations and hospitalizations were compared between disease states and between olanzapine and perphenazine, quetiapine, risperidone, and ziprasidone.. A total of 1,338 patients (SZ + AUD = 22.6%; SZ-only = 77.4%) were included. Time to first exacerbation of SZ was significantly shorter in the SZ + AUD versus SZ-only population (median = 5.4 vs 6.4 months; hazard ratio [HR] = 1.20 [95% CI, 1.01-1.42]; P = .039). Similar findings were observed for first hospitalization (HR = 1.63 [95% CI, 1.20-2.22]; P = .002) and recurrent hospitalizations (HR = 1.60 [95% CI, 1.18-2.15]; P = .002). The most common reasons leading to exacerbation in both groups were an increase in symptom severity and lack of efficacy. In patients with SZ + AUD related or unrelated to marijuana, perphenazine, quetiapine, risperidone, and ziprasidone were associated with significantly shorter time to first exacerbation versus olanzapine.. This post hoc analysis confirmed that patients with SZ + AUD had a worse illness course than patients with SZ-only and suggests that olanzapine may be associated with a longer time to first and recurrent exacerbations versus other antipsychotics in this difficult-to-treat population. Further research is needed to identify effective treatments for this important yet understudied patient population.. ClinicalTrials.gov identifier: NCT00014001.

Topics: Adult; Alcoholism; Antipsychotic Agents; Comorbidity; Female; Hospitalization; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Symptom Flare Up; Thiazoles; Time Factors

Schizophrenia is a severe brain disorder with an excess morbidity and mortality partly due to a higher incidence of metabolic disturbances and cardio-vascular events. The exposure to antipsychotic treatment has been observed linked to these metabolic abnormalities. This study explores the metabolic effects of aripiprazol, quetiapine and ziprasidone in drug-naïve patients with a first-episode of psychosis, at long-term. Two-hundred and two patients with first-episode of psychosis were included in the study. Patients were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Clinical, sociodemographic and anthropometric measures, as well as lipid and glyceamic parameters, were recorded at baseline and after three years of initiating antipsychotic treatment. Body weight and BMI increased significantly after 3 years of follow-up (F = 35.0, p<0.001; and F = 37.6, p<0.001, respectively). Most of the increase in weight occurred within the first year of treatment. The proportion of patients meeting criteria for obesity (5.6% vs 25.7%; p<0.001), hypercholesterolemia (23.2% vs 41.7%; p<0.001) and hypertriglyceridemia (5.8% vs 23.0%; p<0.001) increased significantly. Head-to-head comparisons between antipsychotic groups revealed that the ziprasidone group presented significantly smaller increments in weight (p = 0.034) and BMI (p = 0.020) than aripiprazole group. After 3 years of having presented a first episode of psychosis, patients show significant increments in body weight and BMI, as well as in lipid and glycaemic parameters leading to clinical metabolic disturbances. In this context, the first year is the critical period for weight gain and development of metabolic changes. In this study, ziprasidone produced smaller weight gain than aripiprazole.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Energy Metabolism; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Piperazines; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Time Factors; Weight Gain; Young Adult

To investigate cardiometabolic effects and their predictors in youths with first-episode psychosis (FEP) treated with quetiapine-extended release (ER) versus aripiprazole.. Youths with FEP who were 12 to 17 years of age were randomized to quetiapine-ER or aripiprazole in the 12-week, double-blinded, Tolerability and Efficacy of Antipsychotics (TEA) trial. Primary outcome was change in body weight; secondary outcomes were changes in body mass index (BMI) and waist circumference (WC), blood pressure (BP), heart rate, and lipid and glucose metabolism parameters. Possible predictors of cardiometabolic changes were examined.. Altogether, 113 patients (schizophrenia-spectrum disorders = 93%; age [mean ± SD] = 15.7 ± 1.4 years; male participants = 30.1%) were randomized to quetiapine-ER (n = 55) or aripiprazole (n = 58). Quetiapine-ER led to significant increases in body weight (4.88 kg, 95% CI = 3.92-5.83, p < .0001), BMI z-score (0.43, 95% CI = 0.33-0.53, p < .0001), and WC z-score (0.97, CI = 0.7-1.23, p < .0001). Changes were significantly smaller with aripiprazole (all between-group p values <.0001): body weight: 1.97 kg (CI = 0.97-2.97, p = .0001), BMI z-score: 0.10 (CI = -0.01 to 0.20, p = .0646), and WC z-score: 0.18 (CI = -0.09 to 0.45, p = .1968). Lipid and glucose metabolism parameters increased significantly at week 4 and week 12 only with quetiapine-ER (p range = 0.0001-0.037). Quetiapine-ER was associated with an increased occurrence of obesity, elevated blood lipids and hyperinsulinemia (p range = 0.004-0.039). Early weight gain, obesity, or type 2 diabetes in the family significantly predicted weight and BMI gain at week 12.. In youths with FEP, quetiapine-ER was associated with significantly greater weight gain and adverse changes in metabolic outcomes than was aripiprazole. Early weight gain must be addressed and family lifestyle factors taken into consideration when treating youths with antipsychotics.. Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis (TEA); https://clinicaltrials.gov; NCT01119014.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Body Mass Index; Child; Delayed-Action Preparations; Denmark; Double-Blind Method; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Treatment Outcome; Weight Gain

In patients with schizophrenia, medication adherence is important for relapse prevention, and effective adherence monitoring is essential for treatment planning. A digital medicine system (DMS) has been developed to objectively monitor patient adherence and support clinical decision making regarding treatment choices. This study assesses the acceptance and performance of the DMS in adults with schizophrenia, schizoaffective disorder or first-episode psychosis and in healthcare professionals (HCPs).. This is a multicentre, 8-week, single-arm, open-label pragmatic trial designed using coproduction methodology. The study will be conducted at five National Health Service Foundation Trusts in the UK. Patients 18-65 years old with a diagnosis of schizophrenia, schizoaffective disorder or first-episode psychosis will be eligible. HCPs (psychiatrists, care coordinators, nurses, pharmacists), researchers, information governance personnel, clinical commissioning groups and patients participated in the study design and coproduction. Intervention employed will be the DMS, an integrated system comprising an oral sensor tablet coencapsulated with an antipsychotic, non-medicated wearable patch, mobile application (app) and web-based dashboard. The coencapsulation product contains aripiprazole, olanzapine, quetiapine or risperidone, as prescribed by the HCP, with a miniature ingestible event marker (IEM) in tablet. On ingestion, the IEM transmits a signal to the patch, which collects ingestion and physical activity data for processing on the patient's smartphone or tablet before transmission to a cloud-based server for viewing by patients, caregivers and HCPs on secure web portals or mobile apps.. Approval was granted by London - City and East Research Ethics Committee (REC ref no 18/LO/0128), and clinical trial authorisation was provided by the Medicines and Healthcare products Regulatory Agency. Written informed consent will be obtained from every participant. The trial will be compliant with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines and the Declaration of Helsinki.. NCT03568500; EudraCT2017-004602-17; Pre-results.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Biosensing Techniques; Cloud Computing; Humans; Medical Informatics Applications; Medication Adherence; Mobile Applications; Multicenter Studies as Topic; Olanzapine; Pragmatic Clinical Trials as Topic; Psychiatry; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Tablets; United Kingdom

Topics: Adult; Antipsychotic Agents; Deprescriptions; Female; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Mental Status and Dementia Tests; Olanzapine; Perphenazine; Proportional Hazards Models; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment.. One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment.. After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment.. We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Thiazoles; Triglycerides; Young Adult

The aim of this study was to compare the effect of quetiapine extended release (ER) versus aripiprazole on corrected QT interval (QTc) and QT dispersion (QTd) in youths with first-episode psychosis.. Youths 12-17 years were randomized to quetiapine ER (daily dose range = 50 to 800 mg) or aripiprazole (daily dose range = 2.5 to 30 mg) in a 12-week double-blinded trial and examined at weeks 0, 4, and 12. Primary outcome was QTc change using Hodges formula (QTcH); secondary outcomes included QTcH > 450 ms, QTcH > 500 ms, QTcH change > 60 ms, QTd, and heart rate (HR).. Among 113 randomized youths, follow-up ECG was available for 93 patients (82.3%) (age = 15.8 ± 1.3 years, males = 34.4%, schizophrenia = 67.7%). Quetiapine ER treatment (n = 47) was associated with a significant increase in QTcH of + 6.8 ± 20.2 ms (p = 0.025), while the change from baseline in patients receiving aripiprazole (n = 46) was non-significant (- 3.4 ± 18.9 ms, p = 0.225). One patient in the quetiapine ER group had a QTcH change of + 62.3 ms. Age, sex, smoking, body mass index, and concomitant medication were not significantly associated with QTcH change, but higher baseline potassium was correlated to higher QTcH change in the quetiapine ER group. The HR increased significantly with quetiapine ER (+ 11.0 ± 14.2 bpm, p < 0.001) but not with aripiprazole (- 0.8 ± 12.0 bpm, p = 0.643). QTd did not significantly change with quetiapine ER or aripiprazole.. QTcH and HR increased significantly with quetiapine ER, although changes were small and likely not clinically significant in otherwise healthy patients. QTcH and HR were unchanged with aripiprazole. No significant change in QTd was seen. ClinicalTrials.gov: NCT01119014, EudraCT: 2009-016715-38.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Delayed-Action Preparations; Electrocardiography; Female; Heart Rate; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

The impact of psychosis on the treatment of bipolar depression is remarkably understudied. The primary aim of this study was to compare treatment outcomes of bipolar depressed individuals with and without psychosis. The secondary aim was to compare the effect of lithium and quetiapine, each with adjunctive personalized treatments (APTs), in the psychotic subgroup.. We assessed participants with DSM-IV bipolar depression included in a comparative effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS) and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP). Mixed models were used to assess the course of symptom change, and Cox regression survival analysis was used to assess the time to remission.. Psychotic features were present in 10.6% (n = 32) of the depressed participants (n = 303). Those with psychotic features had higher scores on the BISS before (75.2 ± 17.6 vs. 54.9 ± 16.3; P < .001) and after (37.2 ± 19.7 vs. 26.3 ± 18.0; P = .003) 6-month treatment. The CGI-S-BP yielded similar results. Participants with and without psychosis had similar course of symptom improvement and similar time to remission. There was no significant difference in the treatment outcomes of lithium (n = 11) and quetiapine (n = 21) among the psychotic subgroup.. Bipolar depressive episodes with psychotic features are more severe, and compared to nonpsychotic depressions, present a similar course of improvement. Given the small number of participants presenting psychosis, the lack of statistically significant difference between lithium- and quetiapine-based treatment of psychotic bipolar depressive episodes needs replication in a larger sample.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Comorbidity; Female; Humans; Lithium Compounds; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome; Young Adult

The long-term consequences of discontinuing antipsychotic medication after successful treatment of first-episode psychosis are not well studied. We assess the relation between early maintenance therapy decisions in first-episode psychosis and the subsequent clinical outcome at 10 years.. This is a 10 year follow-up study, spanning Sept 5, 2003, to Dec 30, 2014, of a randomised, double-blind trial in seven centres in Hong Kong in which 178 patients with first-episode psychosis with full positive symptom resolution after at least 1 year of antipsychotic treatment were given maintenance treatment (n=89; oral quetiapine 400 mg daily) or early treatment discontinuation (n=89; placebo) for 12 months. After the trial, patients received naturalistic treatment. Overall this cohort of patients will have received about 3 years of treatment before entering the follow-up phase of the study: about 2 years of maintenance treatment before study entry and 1 year of treatment in the trial. The primary outcome of this follow-up was the proportion of patients in each group (including those for whom direct follow-up was not available) with good or poor long-term clinical outcomes at 10 years, with poor outcome defined as a composite of persistent psychotic symptoms, a requirement for clozapine treatment, or death by suicide. The randomised trial was registered with ClinicalTrials.gov, number NCT00334035, and the follow-up study was registered with ClinicalTrials.gov, number NCT01926340.. Poor 10 year clinical outcome occurred in 35 (39%) of 89 patients in the discontinuation group and 19 (21%) of 89 patients in the maintenance treatment group (risk ratio 1·84, 95% CI 1·15-2·96; p=0·012). Suicide was the only serious adverse event that occurred in the follow-up phase (four [4%] patients in the early discontinuation group vs two [2%] in the maintenance group).. In patients with first-episode psychosis with a full initial response to treatment, medication continuation for at least the first 3 years after starting treatment decreases the risk of relapse and poor long-term clinical outcome.. Food and Health Bureau, Research Grants Council of Hong Kong, and AstraZeneca.

Topics: Adult; Antipsychotic Agents; Clozapine; Double-Blind Method; Female; Follow-Up Studies; Hong Kong; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Schizophrenia; Treatment Outcome; Young Adult

Different effectiveness profiles among second-generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to affect long-term outcome. The aim of this study was to compare the clinical effectiveness of aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.. From October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. Two hundred-two first-episode, drug-naïve patients were randomly assigned to aripiprazole (n=78), ziprasidone (n =62), or quetiapine (n=62) and followed-up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on the intention-to-treat principle was conducted in the analysis for clinical efficacy.. The overall dropout rate at 3 years reached 19.3%. Treatment discontinuation rates were significantly different among treatment groups (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (χ2=11.680; P=.001). Statistically significant differences in terms of nonefficacy, nonadherence, and side effects were observed among treatment groups along the 3-year follow-up determining significant differences in time to all-cause discontinuation (log-rank=32.260; P=.001). Significant differences between treatments were found in the categories of sleepiness/sedation (χ2=9.617; P=.008) and increased sleep duration (χ2=6.192; P=.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines.. First-episode psychosis patients on quetiapine were more likely to discontinue treatment due to nonefficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Young Adult

Acute akathisia is a neuropsychiatric syndrome with a negative effect on illness outcome. Its incidence in patients treated with antipsychotics has shown to be highly variable across studies.. Our goals were to investigate prevalence, risk factors for the development of acute akathisia, and differences in incidence between antipsychotics in a sample of 493 first episode non-affective psychosis patients.. This is a pooled analysis of three prospective, randomized, flexible-dose, and open-label clinical trials. Patients were randomized assigned to different arms of treatment (haloperidol, quetiapine, olanzapine, ziprasidone, risperidone, or aripiprazole). Akathisia was determined using the Barnes Akathisia Scale at 6 weeks after antipsychotic initialization. Univariate analyses were performed to identify demographic, biochemical, substance use, clinical, and treatment-related predictors of acute akathisia. Considering these results, a predictive model based of a subsample of 132 patients was constructed with akathisia as the dependent variable.. The overall incidence of akathisia was 19.5%. No differences in demographic, biochemical, substance use, and clinical variables were found. Significant incidence differences between antipsychotics were observed (Χ. Among second generation antipsychotics, only olanzapine and quetiapine should be considered as akathisia-sparing drugs. The type of antipsychotic, having been hospitalized, and a more severe symptomatology at intake seem to predict the development of acute akathisia.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Piperazines; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Young Adult

Head-to-head trials to guide antipsychotic treatment choices for paediatric psychosis are urgently needed because extrapolations from adult studies might not be implementable. In this superiority trial with two-sided significance testing, we aimed to compare the efficacy and safety of quetiapine-extended release (quetiapine-ER) versus aripiprazole in children and adolescents with first-episode psychosis, to determine whether differences between the two treatments were sufficient to guide clinicians in their choice of one drug over the other.. In this multicentre, double-blind, randomised trial in seven Danish university clinics, we recruited children and adolescents aged 12-17 years with a diagnosis of ICD-10 schizophrenia-spectrum disorder, delusional disorder, or affective-spectrum psychotic disorder, and psychotic symptoms scoring at least 4 on at least one of the following Positive and Negative Syndrome Scale (PANSS) items: P1 (delusions), P2 (conceptual disorganisation), P3 (hallucinations), P5 (grandiosity), P6 (suspiciousness/persecution), and G9 (unusual thought content), and a total PANSS score greater than 60. Patients were randomly assigned (1:1) to 12 weeks of treatment with target doses of 600 mg/day of quetiapine-ER (starting from 50 mg/day) or 20 mg/day of aripiprazole (starting from 2·5 mg/day). The assigned drug was titrated over five levels, with 2 days at each dose, and the final dose achieved on day 9. Randomisation was done using a computer-generated concealed sequence with a block size of 8, and stratified by baseline PANSS positive score (≤20 points or >20 points) and age (12-14 years or 15-17 years). Study drugs were administered in identical capsules, and interventions, assessments, and data analysis were done masked. The primary outcome was PANSS positive score. Key adverse outcomes were bodyweight, homoeostatic model of insulin resistance (HOMA-IR), akathisia, and sedation. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01119014.. Between June 10, 2010, and Jan 29, 2014, 231 participants were assessed for elegibility, of whom 113 were randomly assigned to quetiapine-ER (n=55) or aripiprazole (n=58). PANSS positive score did not differ between groups after 12 weeks (adjusted mean change -5·05 [5·46] for quetiapine-ER, -6·21 [5·42] for aripiprazole; p=0·98), but decreased over time in both groups (p<0·0001). Weight gain was more rapid with quetiapine-ER (p=0·0008), with an adjusted mean weight group difference at week 12 of 3·33 kg (SD 7·23; effect size 0·64; p<0·0001). The HOMA-IR group difference at week 12 favoured aripiprazole (adjusted mean log-transformed group difference 0·259 [SD 0·906]; effect size 0·35; p=0·0060). Akathisia was more common with aripiprazole at week 2 (observed in 34 [60%] of 57 patients; estimated 63·5%) than with quetiapine-ER (15 [30%] of 50; estimated 31·3%; p=0·0021), but not at other timepoints. Sedation proportions did not change significantly over time with either intervention (observed at weeks 2, 4, and 12, respectively, for quetiapine-ER in 43 [83%] of 52, 40 [83%] of 48, and 34 [72%] of 47 patients and for aripiprazole in 49 [89%] of 55, 52 [96%] of 54, and 44 [92%] of 48 patients), and the overall estimated probability combining all timepoints was significantly higher for aripiprazole (97·1%) than for quetiapine-ER (89·2%; p=0·012). In addition to sedation and akathisia, the most common adverse events were tremor (42 [79%] patients in the quetiapine-ER group vs 52 [91%] patients in the aripiprazole group), increased duration of sleep (47 [92%] vs 39 [71%]), orthostatic dizziness (42 [78%] vs 46 [81%]), depression (43 [80%] vs 44 [77%]), tension/inner unrest (37 [69%] vs 50 [88%]), failing memory (41 [76%] vs 44 [77%]), and weight gain (46 [87%] vs 38 [68%]).. This first head-to-head comparison of quetiapine-ER versus aripiprazole in early-onset psychosis showed no significant group differences in severity of psychopathology after 12 weeks of treatment. Quetiapine-ER was associated with more metabolic adverse events and aripiprazole with more initial akathisia and, unexpectedly, more sedation. The limited antipsychotic efficacy and high level of adverse events were noticeable. This trial provides novel information for the treatment of early-onset psychosis and highlights the importance of adverse event profiles when choosing among antipsychotics for children and adolescents who often require chronic treatment.. The National Research Council for Health and Disease Foundation for Health Promotion, AP Møller Foundation, Rosalie Petersens Foundation, Stevn and Rindom Foundation, Foundation for the Promotion of Medical Science, The Capital Region Psychiatric Research Foundation, Tryg Foundation, Region of Southern Denmark Research Foundation, Danish Psychiatric Research Educational Fund, Psychiatry Foundation, Foundation of 17-12-1981, Psychiatric Research Foundation Region Zealand, Capital Region Strategic Research Foundation, Knud og Dagny Andresens Foundation, Psychiatric Research Foundation of 1967, The Capital Region Research Foundation, Dr Sofus Carl Emil Friis and Hustru Olga Friis Scholarship, Tømrerhandler Johannes Fogs Foundation, Brdr Hartmanns Foundation DKK, Aase and Ejnar Danielsens Foundation, Jacob Madsen and wife Olga Madsens Foundation, CC Klestrup and wife Scholarship, Lundbeck Foundation Scholarship, and Tømrermester Jørgen Holm and wife Elisas Scholarship.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Delayed-Action Preparations; Denmark; Double-Blind Method; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Treatment Outcome; Weight Gain

Hyperprolactinemia is considered a troubling adverse effect of antipsychotics. Direct comparisons among second generation antipsychotics are scant in clinical practice. We hypothesize prolactin-sparing second-generation antipsychotics may have differential effects on prolactin levels and that they may be influenced by sex.. To explore the differential effect of three widely used prolactin-sparing antipsychotics, aripiprazole, quetiapine and ziprasidone, on prolactin plasma levels in first episode non-affective psychosis during a 1year of treatment.. From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. 141 patients who were randomly allocated to aripiprazole (N=56), quetiapine (N=36) or ziprasidone (N=49) were analyzed. The main outcome was differences in prolactin plasma levels over 1year follow-up among the three antipsychotics. Prolactin levels had a skewed distribution and therefore they were log-transformed before statistical analyses.. Our findings provide additional evidence of differential effects of three sparing-prolactin antipsychotics on prolactin release and may help clinicians to decide among therapeutic options.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Brief Psychiatric Rating Scale; Cohort Studies; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Piperazines; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Sex Characteristics; Thiazoles; Time Factors; Young Adult

Relapse is distressingly common after the first episode of psychosis, yet it is poorly understood and difficult to predict. Investigating changes in cognitive function preceding relapse may provide new insights into the underlying mechanism of relapse in psychosis. We hypothesized that relapse in fully remitted first-episode psychosis patients was preceded by working memory deterioration.. Visual memory and verbal working memory were monitored prospectively in a 1-year randomized controlled trial of remitted first-episode psychosis patients assigned to medication continuation (quetiapine 400 mg/day) or discontinuation (placebo). Relapse (recurrence of positive symptoms of psychosis), visual (Visual Patterns Test) and verbal (Letter-Number span test) working memory and stressful life events were assessed monthly.. Remitted first-episode patients (n = 102) participated in the study. Relapsers (n = 53) and non-relapsers (n = 49) had similar baseline demographic and clinical profiles. Logistic regression analyses indicated relapse was associated with visual working memory deterioration 2 months before relapse [odds ratio (OR) 3.07, 95% confidence interval (CI) 1.19-7.92, P = 0.02], more stressful life events 1 month before relapse (OR 2.11, 95% CI 1.20-3.72, P = 0.01) and medication discontinuation (OR 5.52, 95% CI 2.08-14.62, P = 0.001).. Visual working memory deterioration beginning 2 months before relapse in remitted first-episode psychosis patients (not baseline predictor) may reflect early brain dysfunction that heralds a psychotic relapse. The deterioration was found to be unrelated to a worsening of psychotic symptoms preceding relapse. Testable predictors offer insight into the brain processes underlying relapse in psychosis.

Topics: Adult; Antipsychotic Agents; Cognitive Dysfunction; Disease Progression; Double-Blind Method; Female; Humans; Male; Memory, Short-Term; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Remission Induction; Stress, Psychological; Time Factors; Young Adult

Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment.. Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients.. A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (N = 83), risperidone (N = 12), quetiapine (N = 46), and ziprasidone (N = 50). At intake, 180 patients were antipsychotic naïve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score ≥60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score ≥60 and only 16.6 % who had a FLI score <30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score ≥60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score ≥ 60, 91.7 %; FLI < 60, 55.9 %; p < 0.001), increased triglyceride levels (FLI score ≥ 60, 54.2 %; FLI < 60, 5.6 %; p < 0.001), decreased HDL levels (FLI score ≥ 60, 41.7 %; FLI < 60, 17.5 %; p = 0.001), hypertension (FLI score ≥ 60, 19.5 %; FLI < 60, 4.5 %; p = 0.002), and waist circumference increase (steatosis 68.8 %; FLI < 60, 14.0 %; p < 0.001).. Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Female; Humans; Incidence; Male; Metabolic Diseases; Middle Aged; Non-alcoholic Fatty Liver Disease; Piperazines; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Young Adult

Clinical observations indicate no cataractogenic potential for quetiapine, in contrast to studies in laboratory animals. This randomized, non-inferiority study compared changes in lens opacity during long-term treatment with quetiapine versus risperidone. Patients with schizophrenia or schizoaffective disorder participated in the 2-year, randomized, multicentre, open-label, ophthalmologist-masked, flexible-dose, parallel-group study. Two ophthalmologists examined each patient 6-monthly for presence of nuclear opalescence (N) and cortical (C) or posterior subcapsular opacification (P), according to the lens opacities classification system II. 1098 patients were randomized to treatment. Mean doses were 386.3 mg/day quetiapine and 3.2 mg/day risperidone. Estimated absolute risk differences in cataractogenic events for quetiapine versus risperidone over 2 years were -0.035 (C), -0.012 (N) and -0.017 (P), with upper margins of confidence intervals within the non-inferiority margin of 10%. In post hoc analysis, risk of any lens opacification event was significantly lower for quetiapine than risperidone (6 and 16 events, respectively; risk difference: -0.058; P = 0.035). Efficacy and other safety assessments were in agreement with known profiles of these medications. Quetiapine was non-inferior to risperidone for changes in lens opacity grade in patients with schizophrenia or schizoaffective disorder, indicating that quetiapine does not have clinically significant cataractogenic potential during long-term treatment.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cataract; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome; Young Adult

A population model describing quetiapine pharmacokinetics (PK) in Western and Chinese patients following oral administration of immediate-release (IR) and extended-release (XR) formulations was developed using plasma concentrations in 127 patients from 5 studies with quetiapine IR and/or XR in Western patients and 1 study with quetiapine XR in Chinese patients. A 1-compartmental model with first-order absorption and first-order elimination adequately described the quetiapine PK. The typical apparent volume of distribution and elimination rate constant of quetiapine were 574 L and 0.12 h(-) (1) , respectively. The estimated population absorption rate constants were 1.46 and 0.10 h(-1) for quetiapine IR and XR, respectively. Covariate analysis revealed that race was not a significant covariate influencing the PK of quetiapine. Simulation conducted with the final quetiapine population PK model predicted that the administration of a 200-mg twice-daily dose of quetiapine IR in Chinese patients would achieve a steady-state AUC (AUCss ) ± standard deviation of 3087 ± 1480 ng · h/mL, which is in close agreement with the reported value (3538 ± 1728 ng · h/mL). The model also predicted that once-daily administration of 300 mg quetiapine IR or XR would achieve similar exposure in terms of AUCss in Chinese patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Asian People; Bipolar Disorder; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Models, Biological; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

The aim of this study was to evaluate the effectiveness of Quetiapine versus Risperidone in control of acute psychotic signs and symptoms in hospitalized patients during four weeks.. In this double-blind, randomized controlled study, a total of 90 patients with a confirmed diagnosis acute psychosis and were hospitalized in Zare Hospital, Sari, Iran, and they were treated with Quetiapine (mean 500 mg/day) or Risperidone (mean 5.2 mg/day), in a 4 week period. The positive and negative symptoms scale (PANSS) and Clinical Global Impression-Severity scale (CGI-s) were used to assess psychotic symptoms and severity of illness in first and the last day of the study.. No significant difference found between two groups in decreasing positive and negative sub-scores in the PANSS. Risperidone was superior to Quetiapine in decreasing the PANSS general psychopathology sub-scores and total score (p<0.05). No significant difference found between two groups in decreasing CGI-s score.

Topics: Acute Disease; Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Young Adult

Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment.. The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year.. From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N = 78), ziprasidone (N = 62), or quetiapine (N = 62) and followed up for 1 year. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.. The overall dropout rate at 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole = 43.6 %, ziprasidone = 66.1 % and quetiapine = 82.3 %) (χ 2 = 22.545; p < 0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ 2 = 19.436; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 30.732 p < 0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants.. First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Female; Humans; Male; Patient Dropouts; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Thiazoles; Treatment Outcome; Young Adult

Depressive symptoms are associated with poor outcomes, increased risk of relapse, and high suicide rates in patients with schizophrenia and schizoaffective disorder. This randomized, open-label, parallel-group, flexible-dose study (NCT00640562) assessed the efficacy of quetiapine extended release (XR) versus risperidone on depressive symptoms in this patient population. Noninferiority of quetiapine XR versus risperidone from baseline to week 12 was assessed by least squares mean (LSM) reduction in the Calgary Depression Scale for Schizophrenia (CDSS). Noninferiority was indicated if the difference in CDSS reductions between quetiapine XR and risperidone had a 95% confidence interval (CI) lower limit of more than -2.7. Overall, 216 patients received quetiapine XR (n = 109; 400-800 mg/day) or risperidone (n = 107; 4-6 mg/day). In the per-protocol population, LSM CDSS reductions for quetiapine XR and risperidone were 8.4 and 6.2 points, respectively (95% CI 0.8-3.7). As the lower limit of the 95% CI was more than -2.7 and the LSM reduction for quetiapine XR was 2.2 points higher than that for risperidone, noninferiority of quetiapine XR versus risperidone was demonstrated. Adverse events for quetiapine XR and risperidone were comparable. In this study, quetiapine XR was noninferior to risperidone at reducing depressive symptoms in patients with schizophrenia or schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Depression; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections.. The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014.. Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size.. ClinicalTrials.gov: NCT01119014.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Patient Selection; Piperazines; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Quinolones; Sample Size; Schizophrenia

This randomized open-label study compared the incidence of metabolic side effects of aripiprazole, ziprasidone and quetiapine in a population of medication-naïve first-episode psychosis patients. A total of 202 subjects were enrolled. Body weight, body mass index, leptin, fasting lipids and fasting glycaemic parameters were measured at baseline and at 3 months follow-up. A hundred and sixty-six patients completed the follow-up and were included in the analyses. A high proportion of patients experienced a significant weight increase (>7% of their baseline weight): 23% ziprasidone (n=12), 32% with quetiapine (n=16) and 45% with aripiprazole (n=31). Patients treated with aripiprazole gained significantly more weight than the patients in the ziprasidone group (1.2 kg [SD=4.1] versus 4.3 kg [SD=4.8], respectively). The increase in leptin levels was greater in women treated with aripiprazole than in those treated with ziprasidone (p=0.030). Mean prolactin levels significantly increased in patients treated with quetiapine and ziprasidone but not in those treated with aripiprazole. Patients treated with quetiapine and aripiprazole showed a significant increase in total cholesterol and LDL-cholesterol plasma levels. Quetiapine-treated patients resulted in a higher increase in LDL-cholesterol than patients treated with ziprasidone (p=0.021). No other significant differences between groups were found. No significant changes in glycaemic parameters were observed. Our results suggest that ziprasidone has a lower liability for inducing weight gain and lipid abnormalities than aripiprazole or quetiapine.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Piperazines; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Sex Factors; Thiazoles; Weight Gain

To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies.. Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were randomized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study: (1) 40 mg/d for 2 weeks; (2) 40 mg/d for 1 week, increased to 80 mg/d on day 8 for week 2 (up-titration group); and (3) 80 mg/d for 2 weeks. Lurasidone was then flexibly dosed (40-120 mg/d) for the subsequent 4 weeks of the study. The preswitch antipsychotic agent was tapered by day 7 to 50% of the original dose and discontinued by the end of week 2. Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as "sedating" (olanzapine or quetiapine) or "nonsedating" (all other antipsychotics). The primary outcome measure was time to treatment failure, defined as any occurrence of insufficient clinical response, exacerbation of underlying disease, or discontinuation due to an adverse event. The study was conducted from June 2010 to May 2011.. Of 240 subjects treated in this study, 86 (35.8%) were treated with an antecedent sedating antipsychotic, and 154 (64.2%) were treated with an antecedent nonsedating antipsychotic. Nineteen (7.9%) of the 240 patients experienced treatment failure. No clinically relevant differences were observed when the 3 randomized switch groups were compared. Treatment failure rates were 10/86 (11.6%) versus 9/154 (5.8%) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication, respectively. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, glucose, insulin, lipids, or prolactin; mean improvements in weight and lipids were observed. Movement disorder rating scales did not demonstrate meaningful changes. The incidence of akathisia as an adverse event was 12.5%; only 1 subject (0.4%) discontinued due to akathisia.. Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks, or 80 mg/d for 2 weeks, or 40 mg/d for 1 week followed by 80 mg/d the second week.. ClinicalTrials.gov identifier: NCT01143077.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Time Factors; Treatment Failure; Treatment Outcome

Differences among antipsychotics in terms of effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different second generation antipsychotics (SGAs) are scarce. We aimed to compare the clinical effectiveness in the short-term of Aripiprazole, Ziprasidone and Quetiapine in the treatment of first-episode schizophrenia-spectrum disorders.. From October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. 202 first-episode drug-naïve patients were randomly assigned to Aripiprazole (N = 78), Ziprasidone (N = 62), or Quetiapine (N = 62) and followed-up for 3 months. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat populations was conducted in the analysis for clinical efficacy.. The overall dropout rate at 3 months was small (13.86%). The treatment discontinuation rate differed significantly between treatment groups (Aripiprazole = 23.1%, Ziprasidone = 37.1% and Quetiapine = 61.3%) (χ(2) = 21.334; p < 0.001). Insufficient efficacy in the group of Quetiapine is the main reason for discontinuation rate differences (χ(2) = 20.223; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 23.467 p < 0.001). Aripiprazole and Quetiapine were associated with a greater depressive symptoms improvement (p = 0.043). The profile of side-effects varies between treatments. Patients on Quetiapine were less likely to be prescribed hypnotics.. Patients treated with Quetiapine had a higher risk of treatment discontinuation in the short-term after a first episode due to insufficient efficacy. Establishing differences between SGAs may help clinicians in prescribing decisions for the treatment of individuals presenting with first-episode schizophrenia.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Outcome Assessment, Health Care; Piperazines; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Thiazoles; Time Factors; Young Adult

Relapse is common among patients with psychotic disorders. Identification of relapse predictors is important for decision regarding maintenance medication. Naturalistic studies often identify medication non-adherence as a dominant predictor. There are relatively few studies for predictors where adherence is already known. It is this situation i.e., discontinuation of medication that predictors will be most useful. We identify predictors for relapse in situations of (i) discontinuation and (ii) continuation of maintenance medication.. Analysis of relapse predictors is based on a randomized controlled study (n=178) comparing relapse rates between patients who discontinued or continued medication for at least 1 year following first-episode psychosis. Demographic, clinical and neurocognitive variables were assessed at baseline as predictors of relapse within 1 year.. Risk of relapse was 79% in the discontinuation group and 41% in the maintenance group. Predictors in the discontinuation group were diagnosis of schizophrenia, poorer semantic fluency performance, and higher blink rate. Predictors in the continuation group were disinhibition soft signs and more general psychopathology symptoms.. Different predictors of relapse were identified for first episode psychosis patients who discontinued and continued maintenance medication. Neurocognitive dysfunctions are important predictors for both groups. While signs of frontal dysfunction and dopamine hyperactivity predict relapse in the discontinuation group, sign of cognitive disinhibition predicts relapse in the continuation group.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Predictive Value of Tests; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Secondary Prevention; Treatment Outcome; Young Adult

Hallucinations are prevalent in schizophrenia and related psychotic disorders and may have severe consequences for the affected patients. Antipsychotic drug trials that specifically address the anti-hallucinatory effectiveness of the respective drugs in representative samples are rare. The aims of the present study were to investigate the rate and severity of hallucinations in acutely admitted psychotic patients at hospital admission and discharge or after 6 weeks at the latest, if not discharged earlier (discharge/6 weeks); and to compare the anti-hallucinatory effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone with up to 2 years' follow-up.. Adult patients acutely admitted to an emergency ward for psychosis were consecutively randomized to risperidone, olanzapine, quetiapine, or ziprasidone and followed for up to 2 years in a pragmatic design. Participants were assessed repeatedly using the hallucinatory behavior item of the Positive and Negative Syndrome Scale (PANSS).. A total of 226 patients, 30.5% of those assessed for eligibility, were randomized and 68% were hallucinating at baseline. This proportion was reduced to 33% at discharge/6 weeks. In the primary analyses based on intention to treat groups of patients experiencing frequent hallucinations, the quetiapine and ziprasidone groups both had faster decreases of the mean hallucination scores than the risperidone group.. Hallucinations are fairly responsive to antipsychotic drug treatment and differential anti-hallucinatory effectiveness may be found among existing antipsychotic drugs. If replicated, this could pave the way for a more targeted pharmacotherapy based on individual symptom profiles, rather than on the diagnostic category.. ClinicalTrials.gov ID; NCT00932529.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Hallucinations; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Cognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis.. Adult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery.. A total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group.. Ziprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome; Young Adult

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease. All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures. PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment. The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Psychomotor Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles; Treatment Outcome; Young Adult

The aim of this naturalistic study was to assess course and predictors of symptomatic remission in outpatients with first-episode psychosis during quetiapine monotherapy.. In 131 outpatients presenting with first-episode psychosis, socio-demographic and clinical variables including PANSS-8 and CGI-S scores were compared at baseline and follow-up between the subgroups with and without symptomatic remission during 12 weeks of flexible-dose treatment with quetiapine.. Logistic regression revealed a low degree of negative symptoms at baseline, younger age, shorter duration of psychotic episode, early treatment response, and the absence of concomitant diseases as predictors for symptomatic remission whereas general disease severity, PANSS-8 total score, gender, alcohol or substance abuse had no predictive value.. Our study underlines the predictive value of early treatment response and a low degree of negative symptoms in outpatients with first-episode psychosis. It also confirms the usability of the symptomatic remission criterion as a cross-sectional threshold criterion in clinical practice.

Topics: Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Outpatients; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Remission Induction; Risk Factors; Symptom Assessment

To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria.. We used equipoise-stratified randomization (a hybrid of complete randomization and clinician's choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010.. Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events.. Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study.. Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients.. ClinicalTrials.gov identifier: NCT00245206.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Therapeutic Equipoise; Triglycerides; United States

The objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation.. This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments.. Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen-Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores.. Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate

Quetiapine is often prescribed at higher than approved doses. We investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d.. A trial was carried out from October 2003-September 2005 in 19 referral centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were randomized on the basis of persistent symptoms of moderate severity (< 30% improvement in total Positive and Negative Syndrome Scale score after ≥ 4 weeks of quetiapine). The 8 week, double-blind study compared continuation of quetiapine 800 mg/d (n = 43) versus 1,200 mg/d (n = 88). The primary outcome measure was emergent or worsening parkinsonism (Simpson-Angus Scale). Secondary outcomes were adverse events, metabolic side effects, and symptom severity.. Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and > 800-mg/d groups, respectively. Emergent or deteriorating parkinsonism in the high-dose group was 3.1% greater (95% CI, -7.8% to 14.0%; P = .76) than in the 800-mg/d group, a value that was within the a priori limit of 16% defined as noninferiority. Both doses of quetiapine were safe and well tolerated. Weight gain was greater in the high-dose group (1.7 kg over 12 weeks; ≥ 7% body weight, n = 11 [12.5%]) versus the 800-mg/d group (1.1 kg over 12 weeks; ≥ 7% body weight, n = 4 [9.3%]). The mean adjusted difference in weight gain (1.3 kg) was greater in the high-dose group (95% CI, 0.0-2.5; P = .044). Symptom severity declined, with no significant difference between groups.. The results did not demonstrate any advantage for use of quetiapine outside the approved dose range.. www.clinicaltrials.gov Identifier: NCT00328978.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Weight Gain

A recent randomized, open-label, relapse prevention trial (ConstaTRE) compared outcomes with risperidone long-acting injectable (RLAI) versus the oral atypical antipsychotic quetiapine. This study also included a small descriptive arm in which patients could also be randomized to aripiprazole. Results of this exploratory analysis are described here. Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or an oral conventional antipsychotic were randomized to RLAI or aripiprazole. Efficacy and tolerability were monitored for up to 24 months. A total of 45 patients were treated with aripiprazole (10-30 mg/day) and 329 patients with RLAI (25-50 mg i.m. every 2 weeks). Relapse occurred in 27.3% (95% CI: 15.0-42.8%) of aripiprazole-treated and 16.5% (95% CI: 12.7-21.0%) of RLAI-treated patients. Kaplan-Meier estimates of mean (standard error) relapse-free period were 313.7 (20.4) days for aripiprazole and 607.1 (11.4) days for RLAI patients. Remission was achieved by 34.1% (95% CI: 20.5-49.9%) of aripiprazole and 51.1% (95% CI: 45.5-56.6%) of RLAI patients. Clinical global impression-change was improved ("minimally improved" to "very much improved") in 26.4% with RLAI and 15.9% with aripiprazole patients. Tolerability was generally good for both treatment groups. Weight gain (7.0% with RLAI vs. 4.4% with aripiprazole), extrapyramidal adverse events (AEs) (10.3% vs. 4.4%), and potentially prolactin-related AEs (4.6% vs. 0%) were more common with RLAI treatment, and gastrointestinal disorders were more common in aripiprazole-treated patients (22.2% vs. 6.1%). Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was numerically longer in RLAI-treated patients than in aripiprazole-treated patients although not statistically significant. Both treatments were generally well tolerated.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Drug Delivery Systems; Female; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Schizophrenia; Secondary Prevention; Time Factors

Twenty-three adolescents with psychotic disorders, aged from 13 to 18 years, participated in a 12-week open label trial (17 adolescents completed the study) in order to examine the impact of quetiapine on clinical status and cognitive functions (encompassing processing speed, attention, short-term memory, long-term memory and executive function). An improvement in Clinical Global Impression and Positive and Negative Symptom Scale (P's ≤ 0.001) was observed. In addition, after controlling for amelioration of symptoms, a significant improvement was observed on one executive function (P = 0.044; Trail Making Part B). The remaining cognitive abilities showed stability. In addition, we observed an interaction between quetiapine doses (>300 mg/day or <300 mg/day) and time, where lower doses showed more improvement in verbal short-term memory (P = 0.048), inhibition abilities (P = 0.038) and positive symptoms (P = 0.020). The neuropsychological functioning of adolescents with psychotic disorders remained mainly stable after 12 weeks of treatment with quetiapine. However, lower doses seemed to have a better impact on two components of cognition (inhibition abilities and verbal short-term memory) and on positive symptoms.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Nootropic Agents; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs, with that of haloperidol in never-treated patients with first-episode psychosis. In total, 114 patients without life time exposure to any psychotropic medication were randomized to haloperidol, olanzapine, risperidone, quetiapine or ziprasidone. Primary outcome was time to all-cause discontinuation. Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale (PANSS). The overall discontinuation rate 64%. At 12 months, the proportion of patients discontinuing treatment was 40.0% for olanzapine, 56.5% for quetiapine, 64.0% for risperidone, 80.0% for ziprasidone and 85.7% for haloperidol. Mean time to antipsychotic discontinuation was higher in patients randomized to second-generation antipsychotics than in those taking haloperidol. Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol, or ziprasidone. Our results suggest that olanzapine might lead to longer treatment continuation in treatment naïve FEP patients than haloperidol and, possibly ziprasidone. Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n =26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n =16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Neuropsychological Tests; Olanzapine; Psychometrics; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Spain; Treatment Outcome

There is a need for more studies on the clinical effectiveness, tolerability and pharmacokinetics of atypical antipsychotics in adolescents with psychotic disorders, as this represents a vulnerable and difficult population to treat. According to recent concerns regarding disabling side effects of antipsychotics, particularly weight gain, further monitoring of their safety profiles is needed. This situation prompted the authors to carry out an investigation on the clinical effectiveness of quetiapine in psychotic adolescents.. 23 adolescents (13-18 years old) with psychotic disorders participated in a 12-week open label trial, including 6 visits assessing clinical efficacy, tolerability and safety of quetiapine (50-750 mg daily).. Adolescents were treated with lower doses compared to adults. Significant decreases in CGI and PANSS total scores were observed after both 4 and 12 weeks of quetiapine treatment compared to baseline. Sedation was the main adverse effect, but medication was generally well tolerated. Irregular compliance, (as assessed by pill counts, a questionnaire and by plasma quetiapine concentration monitoring), and alcohol and/or cannabis consumption were factors identified in this study which add to the difficulty in treating this population.. The results of the present study help to consolidate evidence of the usefulness of quetiapine as a treatment for adolescents with psychotic disorders. However, this study also highlights the issues encountered in treating this group, including the presence of comorbidities such as drug abuse.

Topics: Adolescent; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Mental Disorders; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Research Design; Surveys and Questionnaires

Quetiapine is often prescribed at doses higher than those approved by regulatory authorities, with limited evidence from controlled trials. The objective of this study was to assess the safety, tolerability, and efficacy of high-dose quetiapine (1200 mg/d) compared with a standard dose of 600 mg/d among patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder hospitalized at 2 state-operated psychiatric facilities. In order to be eligible for randomization, subjects were required to prospectively fail to demonstrate an initial therapeutic response during a 4-week run-in phase with quetiapine at 600 mg/d (immediate release and dosed twice a day). Lack of an adequate initial response was defined a 15% or lower decrease in the Positive and Negative Syndrome Scale total score. Patients were then randomized to either continue quetiapine at 600 mg/d for an additional 8 weeks or to receive 1200 mg/d quetiapine instead. No significant differences were observed between the high dose (n = 29) and standard dose (n = 31) groups in change from baseline to endpoint on extrapyramidal symptoms, electrocardiographic changes, or most laboratory measures between groups. There was a significant difference between groups for triglycerides (P = 0.035), and post hoc tests revealed a decrease in triglycerides from baseline (mean [SD], 162.7 [59.3] mg/dL) to endpoint (mean [SD], 134.8 [62.7] mg/dL) for the 600 mg/d group (P = 0.019). The mean change in the Positive and Negative Syndrome Scale total score did not differ between groups. In conclusion, quetiapine at 1200 mg/d, although reasonably tolerated, did not confer any advantages over quetiapine at 600 mg/d among patients who had failed to demonstrate an adequate response to a prospective 4-week trial of 600 mg/d.

Topics: Adult; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

The objectives of this study were to evaluate the effects of switching from quetiapine to ziprasidone on weight, safety, and effectiveness. In this study, 241 subjects with schizophrenia or schizo affective disorder who had been treated with quetiapine (≥300 mg/day) for ≥3 months with either suboptimal efficacy or poor tolerability were enrolled in a 16-week, open-label, flexible-dose trial, with a 16-week follow-up (total 32 weeks). Quetiapine was tapered and discontinued over the course of 2 weeks, while ziprasidone was titrated up and dosed at 40-80 mg b.i.d. The primary endpoint was weight change (kg) from baseline at 16 weeks. Secondary endpoints were change in waist/hip circumference, lipid profile, fasting glucose, and glycosylated hemoglobin (HbA1c). Additional secondary endpoints included changes in scores on the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions Improvement and Severity Scales (CGI-I and CGI-S), the Calgary Depression Scale for Schizophrenia (CDSS), the Schizophrenia Cognition Rating Scale (ScoRS), and the Global Assessment of Functioning (GAF). Safety measures included adverse event (AE) reporting and administration of the Abnormal Involuntary Movement Scale (AIMS).. At week 16, there was a small but statistically significant decrease in weight, with a mean change from baseline of -0.73 kg (1-sided 95% upper confidence bound=-0.33) using the last observation carried forward [LOCF] approach. There were small mean decreases in levels of total cholesterol, low density lipoprotein (LDL), and triglycerides at week 16, but no change in fasting glucose or HbA1c. At week 16, there were also significant changes indicating improvement in the secondary clinical assessments, including the PANSS scores, CGI-S, CDSS, SCoRS and GAF. There was no change in the AIMS. AEs included insomnia (12.4%), somnolence (13.7%), and nausea (9.1%).. Subjects switching from quetiapine to ziprasidone showed a small but significant decrease in weight as well as improved lipid profiles, regardless of their metabolic status and disease severity at baseline. Subjects also showed improvement in clinical symptoms and in cognitive functioning. Ziprasidone, with a comparatively neutral metabolic profile relative to other antipsychotics, may be an effective treatment alternative for patients experiencing weight gain or lack of tolerability with quetiapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Blood Glucose; Body Weight; Cholesterol; Cognition; Dibenzothiazepines; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Outpatients; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome; Triglycerides; Young Adult

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. The use of anti-PD medications has been the most widely identified risk factor for PD psychosis (PDP). However, the pathophysiology of PDP remains unclear. Although the efficacy of electroconvulsive therapy (ECT) for PD had been pointed out, only one study has demonstrated the effectiveness of ECT on both psychotic symptoms and motor symptoms. The aim of this study was to examine the acute effectiveness of ECT on PD and to identify the brain areas associated with PDP.. The study was conducted at Juntendo University Hospital in Tokyo. Eight patients with L-DOPA- or dopamine (DA) agonist-induced PDP, who were resistant to quetiapine treatment, were enrolled. Severity of PD was evaluated using the Hoehn and Yahr stage. Psychotic symptoms were evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS). Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc ECD SPECT) was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. A voxel-by-voxel group analysis was performed using Statistical Parametric Mapping (SPM5).. Our study clearly demonstrated that PDP was significantly less severe after ECT than before ECT, as indicated by change in mean SAPS total domain score (t=7.2, P=0.0002). Furthermore, the patients showed significant improvement in Hoehn and Yahr stage after ECT (t=11.7, P<0.0001). A further notable observation was significant increase in rCBF in the right middle frontal gyrus after ECT.. We conclude that a course of ECT produced notable improvements not only in PDP but also in the severity of PD. The findings of change in rCBF suggest implications for dysfunction in the middle frontal region for patients with PDP.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clinical Trials, Phase I as Topic; Dibenzothiazepines; Disease Progression; Electroconvulsive Therapy; Electroencephalography; Female; Humans; Inpatients; Levodopa; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Regional Blood Flow; Risk Factors; Time Factors; Tokyo; Tomography, Emission-Computed, Single-Photon

The authors conducted a multisite randomized controlled trial examining the strategy of switching from olanzapine, quetiapine, or risperidone to aripiprazole to ameliorate metabolic risk factors for cardiovascular disease.. Patients with schizophrenia or schizoaffective disorder with a body mass index ≥ 27 and non-high-density lipoprotein (non-HDL) cholesterol ≥ 130 mg/dl who were on a stable treatment dosage of olanzapine, quetiapine, or risperidone were randomly assigned to switch to ari-piprazole (N=109) for 24 weeks or stay on their current medication (N=106). All participants were enrolled in a behaviorally oriented diet and exercise program. Clinical raters were blinded to treatment assignment. The primary and key secondary outcomes were change in non-HDL cholesterol and efficacy failure, respectively.. The prespecified primary analysis included 89 switchers and 98 stayers who had at least one postbaseline non-HDL cholesterol measurement. The least squares mean estimates of non-HDL cholesterol decreased more for the switch group than for the stay group (-20.2 mg/dl and -10.8 mg/dl, respectively). Switching was associated with larger weight reductions (least squares mean=2.9 kg) and a net reduction of serum triglycerides of 32.7 mg/dl. Twenty-two switchers (20.6%) and 18 stayers (17.0%) experienced protocol-defined efficacy failure. Forty-seven switchers (43.9%) and 26 stayers (24.5%) discontinued the assigned antipsychotic medication before 24 weeks.. Switching to aripiprazole led to improvement of non-HDL cholesterol levels and other metabolic parameters. Rates of efficacy failure were similar between groups, but switching to aripiprazole was associated with a higher rate of treatment discontinuation. In the context of close clinical monitoring, switching from an antipsychotic with high metabolic risk to one with lower risk to improve metabolic parameters is an effective strategy.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Body Weight; Cholesterol; Cholesterol, LDL; Combined Modality Therapy; Dibenzothiazepines; Diet, Reducing; Drug Substitution; Exercise; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk; Risperidone; Schizophrenia; Treatment Outcome; Triglycerides

To compare the effects of haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on hostility in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder.. We used the data acquired in the European First-Episode Schizophrenia Trial, an open, randomized trial (conducted in 14 countries) comparing 5 antipsychotic drugs in 498 patients aged 18-40 years with first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. DSM-IV diagnostic criteria were used. Patients were assessed between December 23, 2002 and January 14, 2006. Most subjects joined the study as inpatients and then continued with follow-ups in outpatient clinic visits. The Positive and Negative Syndrome Scale (PANSS) was administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. We analyzed the scores on the PANSS hostility item in a subset of 302 patients showing at least minimal hostility (a score > 1) at baseline. We hypothesized (1) that the treatments would differ in their efficacy for hostility and (2) that olanzapine would be superior to haloperidol. Our primary statistical analysis tested the null hypothesis of no difference among the treatment groups in change in hostility over time. Secondary analysis addressed the question of whether the effects on hostility found in the primary analysis were specific to this item. All our analyses were post hoc.. The primary analysis of hostility indicated an effect of differences between treatments (F(4,889) = 4.02, P = .0031). Post hoc treatment-group contrasts for hostility change showed that, at months 1 and 3, olanzapine was significantly superior (P < .05) to haloperidol, quetiapine, and amisulpride in reducing hostility. Secondary analyses demonstrated that these results were at least partly specific to hostility.. Both hypotheses were supported. Olanzapine appears to be a superior treatment for hostility in early phases of therapy for first-episode schizophrenia, schizoaffective disorder, and schizophreniform disorder. This efficacy advantage of olanzapine must be weighed against its adverse metabolic effects and propensity to cause weight gain.. ISRCTN Register Identifier: ISRCTN68736636.

Topics: Adult; Aggression; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Haloperidol; Hostility; Humans; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles; Treatment Outcome

Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis.. Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale-Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS).. A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01).. There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis.. ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Benzodiazepines; Depression; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles

A 2-week, randomized, parallel-group open trial was designed to evaluate the safety and tolerability of a rapid initiation regimen with a higher dose of quetiapine (up to 800 mg/d by Day 4) than that used in the conventional initiation regimen of quetiapine (up to 400mg/d by Day 5) in patients with schizophrenia or schizoaffective disorders. Forty patients were recruited and randomly (3:1) assigned to either the group with rapid initiation of quetiapine or the group with conventional initiation. At the end of the investigation, the difference between the groups in the incidence of adverse events was not significant; a significant drop in the Barnes Akathisia Rating Scale and Simpson-Angus Scale scores was observed only in the group with the rapid initiation regimen. The groups did not differ in terms of improvement on the Clinical Global Impression-Severity of Illness and Positive and Negative Syndrome Scale at the end of the study. The results of our 2-week study suggest that rapid initiation with a higher dose of quetiapine (up to 800 mg/d by Day 4) is well tolerated in patients with schizophrenia or schizoaffective disorders and does not compromise efficacy relative to the conventional initiation.

Topics: Adult; Antipsychotic Agents; Constipation; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Treatment Outcome; Young Adult

Schizophrenia patients have a potential increased risk of metabolic dysregulation during antipsychotic treatments. Our objective was to compare changes in prolactin and metabolic variables (glucose, lipids and weight) as a post-hoc analysis from a six-month, randomised, controlled study of olanzapine (OLZ, n = 171; 10-20 mg/day) or quetiapine (QUE, n = 175; 300-700 mg/day). No statistically significant treatment group differences for baseline to endpoint mean changes in body mass index (P = 0.209) or weight (P = 0.250) were observed. There was a greater incidence of clinically significant weight gain (defined as > or =7% increase from baseline) in OLZ (19.2%) compared to QUE (13.2%)-treated patients (P = 0.181). No statistically significant treatment group differences for lipids and glucose variables, either as mean change from baseline to endpoint or treatment-emergent (TE) categorical changes were found (P > or = 0.05). Incidence rates for TE diabetes were similar between treatment groups 2.5% (n = 4) in the OLZ-treatment group and 1.3% (n = 2) in the QUE-treatment group (P = 0.685). Hyperprolactinaemia was present at baseline in many patients (OLZ 32.9%; QUE 31.4%), but after 2 weeks of treatment prolactin values had reverted to normal for nearly all patients (OLZ 100%; QUE 99.4%). There were no significant treatment differences in any variable between cohorts.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lipid Metabolism; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Weight Gain

The objective of this study was to evaluate the efficacy and tolerability of quetiapine in the treatment of first onset psychosis in older adolescents using risperidone as a comparator. Twenty-two patients with first onset psychosis were randomized to receive quetiapine (up to 800 mg/day) or risperidone (up to 6 mg/day) for 6 weeks. Raters blind to treatment assignment performed outcome symptom ratings. No statistical differences emerged in terms of efficacy or tolerability between the two drugs. However, there were some clinically notable differences that seem to favour the efficacy of risperidone over quetiapine. Patients taking quetiapine, although improved, showed less clinical improvement on scores for total positive and negative symptoms, clinical global severity and depression at 6 weeks than patients taking risperidone. Although both treatments were associated with weight gain and sedation, more patients on quetiapine experienced over 10% weight gain. However, fewer patients who were taking quetiapine required anticholinergic medication or experienced extrapyramidal side effects than patients taking risperidone. Risperidone was significantly more likely to be associated with elevation in serum prolactin levels in this population. In conclusion, the results in this small trial show that adolescent patients may benefit more from treatment with risperidone than quetiapine. However, those susceptible to side effects, particularly hyperprolactinaemia, may be more suitable for treatment with quetiapine.

Topics: Adolescent; Adolescent Behavior; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome; Weight Gain

No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.. Patients >or= 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.. A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.. Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.. ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Galactorrhea; Hospitalization; Humans; Length of Stay; Male; Olanzapine; Patient Readmission; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Thiazoles; Treatment Outcome

The ACCESS trial examined the 12-month effectiveness of continuous therapeutic assertive community treatment (ACT) as part of integrated care compared to standard care in a catchment area comparison design in patients with schizophrenia spectrum disorders treated with quetiapine immediate release.. Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT as part of integrated care (n = 64) or standard care (n = 56) to 120 patients with first- or multiple-episode schizophrenia spectrum disorders (Structured Clinical Interview for DSM-IV Axis I Disorders criteria); multiple-episode patients were restricted to those with a history of relapse due to medication nonadherence. The primary outcome was time to service disengagement. Secondary outcomes comprised medication nonadherence, improvements of symptoms, functioning, quality of life, satisfaction with care from patients' and relatives' perspectives, and service use data. The study was conducted from April 2005 to December 2008.. 17 of 120 patients (14.2%) disengaged with service, 4 patients (6.3%) in the ACT and 13 patients (23.2%) in the standard care group. The mean Kaplan-Meier estimated time in service was 50.7 weeks in the ACT group (95% CI, 49.1-52.0) and 44.1 weeks in the standard care group (95% CI, 40.1-48.1). This difference was statistically significant (P = .0035). Mixed models repeated measures indicated larger improvements for ACT compared to standard care regarding symptoms (P < . 01), illness severity (P < . 001), global functioning (P < . 05), quality of life (P < . 05), and client satisfaction as perceived by patients and family (both P < . 05). Logistic regression analyses revealed that ACT was associated with a higher likelihood of being employed/occupied (P = .001), of living independently (P = .007), and of being adherent with medication (P < . 001) and a lower likelihood of persistent substance misuse (P = .027).. Compared to standard care, intensive therapeutic ACT as part of integrated care could improve 1-year outcome. Future studies need to address in which settings these improvements can be sustained.. clinicaltrials.gov Identifier: NCT01081418.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Community Mental Health Services; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Patient Discharge; Patient Satisfaction; Proportional Hazards Models; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index

Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan-Meier estimate of time-to-relapse was significantly longer with RLAI (p<0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25±6.61 and 0±6.55 kg, respectively. There were no significant between-group differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients randomized to RLAI compared with those randomized to oral quetiapine. Both antipsychotics were generally well tolerated.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Injections, Intramuscular; Male; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Secondary Prevention

To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment.. 12 month randomised, double blind, placebo controlled trial.. Early psychosis outpatient clinics in Hong Kong.. 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.. Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.. Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.. 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; chi(2)=3.20, df=1; P=0.07).. In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year. Trial registration Clinical trials NCT00334035.

Topics: Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Time Factors; Treatment Outcome

To compare the efficacy, safety, and tolerability of olanzapine and quetiapine in adolescents with first episode psychosis.. Fifty adolescents (age 16 +/- 1.25) with a first episode of psychosis were randomized to quetiapine or olanzapine in a 6-month open label study. Efficacy and side effect scales, as well as vital signs and laboratory data were recorded at baseline, 7, 15, 30, 90, and 180 days (end of study).. Out of the total sample included in the study, 32 patients completed the trial (quetiapine n = 16, olanzapine n = 16). Patients in both treatment groups had a significant reduction in all clinical scales with the exception of the negative scale of the Positive and Negative Symptom Scale (PANSS) for olanzapine and the general psychopathology scale of the PANSS for quetiapine. The only difference between treatment arms on the clinical scales was observed on the patients' strength and difficulties questionnaire (SDQ) scale, with greater improvement for olanzapine. Patients on olanzapine gained 15.5 kg and patients on quetiapine gained 5.5 kg.. Olanzapine and quetiapine reduced psychotic symptoms in this adolescent sample. Patients on olanzapine gained significantly more weight. Side effects with both drugs seemed to be more prevalent than those reported in adult studies.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Surveys and Questionnaires

An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome. However, factors that predict treatment response are not well understood. The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis (FEP) patients.. We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate. Logistic regression was used to examine predictors of treatment response. Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial.. Larger pituitary volume was associated with less improvement in overall psychotic symptoms (Brief Psychiatric Rating Scale (BPRS) P=0.031) and positive symptoms (BPRS positive symptom subscale P=0.010). Regardless of gender, patients with a pituitary volume at the 25th percentile (413 mm(3)) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile (635 mm(3)) (odds ratio=3.07, CI: 0.90-10.48).. The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis. Potential implications for treatment strategies in early psychosis are discussed.

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Imaging, Three-Dimensional; Logistic Models; Magnetic Resonance Imaging; Male; Models, Statistical; Pituitary Gland; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Young Adult

Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder.. In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score.. 323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P = .942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (-12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (-18.7 ng/mL vs -1.9 ng/mL; P < .001) but not in the quetiapine subgroup (-3.01 ng/mL vs +0.15 ng/mL; P = .104).. The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia.. clinicaltrials.gov Identifier: NCT00325689.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Aripiprazole; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Fatigue; Female; Headache; Humans; Male; Piperazines; Placebos; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Treatment Outcome

The present study explores sweet stimuli effects on hunger and negative alliesthesia in patients treated with antipsychotic drugs and controls. Those phenomena were examined in relation to previous weight gain, eating and weight-related cognitions and type of sweet stimuli: aspartame or sucrose. Alliesthesia is delayed in participants who gained weight regardless of cross group differences. A similar reduction of hunger was observed after the intake of two kinds of sweet stimuli (aspartame or sucrose) whereas alliesthesia measures were not affected. Whereas atypical antipsychotic drug-induced weight gain is linked to delayed satiety, the phenomenon is similar in magnitude in non-psychiatric controls who gained weight.

Topics: Adult; Antipsychotic Agents; Aspartame; Benzodiazepines; Carbonated Beverages; Clozapine; Dibenzothiazepines; Double-Blind Method; Food Preferences; Humans; Hunger; Male; Middle Aged; Olanzapine; Pleasure; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sucrose; Surveys and Questionnaires; Sweetening Agents; Taste; Time Factors; Young Adult

The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior.. The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals.. In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo.. In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.

Topics: Activities of Daily Living; Aged; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Surveys and Questionnaires

The aim of this study was to evaluate metabolic and hormonal side effects in children and adolescents after 6 months of treatment with 3 different second-generation antipsychotics (SGAs).. 66 children and adolescents (44 male [66.7%], mean +/- SD age = 15.2 +/- 2.9 years) treated for 6 months with risperidone (N = 22), olanzapine (N = 20), or quetiapine (N = 24) composed the study sample. 34 patients (51.5%) suffered from schizophrenia or other psychosis (according to DSM-IV criteria). Patients were consecutively attending different programs from March 2005 to October 2006. Prior to enrollment in the study, patients were either antipsychotic-naive (37.9%, N = 25) or had been taking an antipsychotic drug for fewer than 30 days. Significant weight gain was defined as a > or = 0.5 increase in body mass index (BMI) z score (adjusted for age and gender) at 6 months. Based on recent criteria for pediatric populations, patients were considered "at risk for adverse health outcome" if they met at least 1 of the following criteria: (1) > or = 85th BMI percentile plus presence of 1 or more negative weight-related clinical outcomes, or (2) > or = 95th BMI percentile.. After the 6 months, BMI z scores increased significantly in patients receiving olanzapine and risperidone. At the 6-month follow-up, 33 patients (50.0%) showed significant weight gain. The number of patients at risk for adverse health outcome increased from 11 (16.7%) to 25 (37.9%) (p = .018). The latter increase was significant only in the olanzapine group (p = .012). Total cholesterol levels increased significantly in patients receiving olanzapine (p = .047) and quetiapine (p = .016). Treatment with quetiapine was associated with a significant decrease in free thyroxin (p = .011).. Metabolic and hormonal side effects of SGAs in children and adolescents should be carefully monitored when prescribing these drugs.

Topics: Adolescent; Benzodiazepines; Blood Glucose; Body Mass Index; Child; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance-Related Disorders; Thyroxine; Triglycerides

The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a naturalistic longitudinal study of early-onset first psychotic episodes. This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months.. Participants were 110 patients, aged 9-17 years, with a first psychotic episode attended consecutively at six different centers. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions (CGI), Disability Assessment Schedule (DAS), and Global Assessment of Function (GAF) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale only at 6 months.. Diagnoses at baseline were 38.2% psychotic disorder not otherwise specified, 39.1% schizophrenia-type disorder, 11.8% depressive disorder with psychotic symptoms, and 10.9% bipolar disorder, manic episode with psychotic symptoms. The most frequently used antipsychotic agents were risperidone (n = 50), quetiapine (n = 18), and olanzapine (n = 16). Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms. Using the baseline score as covariate, no significant differences were found in the reductions on any scale in patients treated with risperidone, quetiapine, or olanzapine for 6 months. Weight increase was greater with olanzapine than with risperidone (p = 0.020) or quetiapine (p = 0.040). More neurological side effects appeared with risperidone than with olanzapine (p = 0.022). All side effects were mild or moderate.. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, are the most used in our context in first psychotic episodes in children and adolescents. These three obtain similar clinical improvement, but differ in their side effects.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Olanzapine; Practice Patterns, Physicians'; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Treatment Outcome; Weight Gain

To assess the effectiveness of aripiprazole in the treatment of patients with psychotic symptoms in the emergency psychiatric setting.. We considered all patients admitted to a psychiatric intensive care unit of a general hospital in a two year-period, treated with at least one dose of aripiprazole. We measured 1) the rate of cases starting aripiprazole who did not change antipsychotic in the course of hospitalization; 2) the rate of cases who were concurrently treated with another antipsychotic; 3) the CGI Improvement score.. In 63 cases, aripiprazole was started on admission. Forty-nine (77.7%) of these cases were treated with aripiprazole also on discharge. Among the 63 cases who started aripiprazole on admission, 22 (34.9%) were concurrently treated with another antipsychotic. Among the 53 cases discharged with aripiprazole, 15 (28.3%) were concurrently treated with another antipsychotic. Of the 49 cases treated with aripiprazole both on admission and on discharge, 24 cases were much improved, 11 cases moderately improved, 10 cases mildly improved, and 4 cases were not improved at the CGI Improvement Score.. Aripiprazole should be considered as first line treatment in some patients affected by psychotic disorders visited in the emergency psychiatric setting.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Therapy, Combination; Emergency Services, Psychiatric; Female; Humans; Intensive Care Units; Male; Middle Aged; Piperazines; Psychiatric Department, Hospital; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

To assess dosing, efficacy, and tolerability of quetiapine fumarate in drug-naive first-episode psychosis.. We present a prospective, randomized, controlled, single-center, double-blind, fixed-dose, 4-week comparison study of 200 mg/day versus 400 mg/day of quetiapine in 141 drug-naive acutely ill first-episode psychosis patients (diagnosed according to DSM-IV) aged 15 to 25 years. The double-blind 4-week trial (Part 1) was followed by a single-blind, naturalistic, flexible-dose 8-week period (Part 2). The main outcome measures were symptomatic change, functioning, and tolerability. Data were collected from July 2003 until January 2006.. The estimated time trends of the linear mixed-effects modeling indicated that efficacy between the 2 treatment groups in Part 1 was similar for most outcome measures except for 5 measures: the Scale for the Assessment of Negative Symptoms (SANS) anhedonia-asociality subscale (p = .011), the Social and Occupational Functioning Assessment Scale (p = .020), the Global Assessment of Functioning scale (p = .070), the SANS affective flattening or blunting subscale (p = .051), and the Udvalg for Kliniske Undersogelser total (p = .056), suggesting that the 200-mg group improved more for the SANS anhedonia-asociality subscale, whereas the 400-mg group showed a slight deterioration. Social and global functioning also improved more in the 200-mg group than in the 400-mg group. Part 2 of the study revealed that, independent of the initial target dose, when clinicians were able to adjust the dose flexibly, the dose at 12 weeks was similar between groups and averaged 268 mg/day.. Our study in acutely ill drug-naive first-episode psychosis patients suggests that quetiapine is a safe and well-tolerated antipsychotic medication. In contrast to multiepisode patients, dosing should be more conservative in untreated new-onset cases. An initial dose of 250 to 300 mg/day of quetiapine is proposed as a primary target dose in drug-naive first-episode psychosis patients.. clinicaltrials.gov Identifier: NCT00449397.

Topics: Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Linear Models; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate

The aim of the study was to assess the efficacy, tolerability and safety of the own developed generic quetiapine, Ketilept (EGIS Pharmaceutical Ltd, Budapest) in patients with an acute episode of schizophrenia and schizoaffective disorder.. These was a multicenter, non comparative, open label, 12-week trial on oral generic quetiapine conducted in 110 patients with DSM-IV acute schizophrenia or schizoaffective disorder. Patients received Ketilept 50 mg on day 1, 100 mg on day 2, 200 mg on day 3, 300 mg on day 4. The flexible dosing (150-750 mg/day) started on day 5. Patients were evaluated at baseline, at day 7, 14, 28 and 84. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Subjective Well-being on Neuroleptics Scale (SWN), Simpson-Angus Extrapyramidal Rating Scale (SAS), Barnes Akathisia Rating Scale (BARS) and UKU Side Effects Rating Scale (UKU). Changes in overall body weight, body mass index (BMI) and abdominal circumference were also evaluated.. After 12 weeks on Ketilept therapy, significant improvements were observed on all major symptoms measures and subscales. 44 (44%) of patients were rated much or very much improved on CGI-I at week 12. The mean SAS and BARS score significantly reduced during the generic quetiapine treatment period (p = 0.0001, p = 0.001). No change was found in the body weight, BMI and abdominal circumference during treatment with Ketilept for 12 weeks. The most common side effects were sedation, and dizziness. 14 adverse events occurred in 6 subjects (5%), of whom 3 patients (2.7%) encountered 3 serious adverse events. The adverse events were mainly mild and moderate. 103 patients (93.6)% completed the study, 2 patients (1.8%) were discontinued from the study due to serious adverse events (insufficient clinical response, sedation).. Despite the limitations of the design, our results suggest that the generic quetiapine, Ketilept in patients with acute schizophrenia and schizoaffective disorder is therapeutic equivalent to the innovator drug in terms of efficacy, tolerability and safety.

Topics: Acute Disease; Aged; Body Mass Index; Body Weight; Dibenzothiazepines; Drug Therapy, Combination; Drugs, Generic; Fatigue; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep; Time Factors; Treatment Outcome; Waist Circumference

Treating elderly patients with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents. Quetiapine is an atypical antipsychotic agent that warrants further investigation.. To assess tolerability, safety, and clinical benefit of quetiapine in AD patients with BPSD.. AD patients with BPSD participated in a 6-week randomized, double-blind, placebo-controlled trial. Quetiapine was increased on the basis of clinical response and tolerability. Primary efficacy assessments included the Neuropsychiatric Inventory (NPI) and Clinical Global Impression of Change (CGI-C). Secondary efficacy measures included the Mini-Mental State Examination (MMSE), the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS).. Forty patients (26 women), mean age 82.2 (SD 6.4) years were enrolled, 27 completed treatment. Median dose of quetiapine was 200 mg/day. Significant NPI total scores reductions (79% for placebo and 68.5% for quetiapine) were observed. The CGI-C score decreased significantly in the quetiapine group (p = 0.009 at 6 weeks) and did not change significantly in the placebo group (p = 0.48). The MMSE, AIMS, SAS scores and adverse events did not differ significantly between the two arms.. Quetiapine did not significantly improve psychosis scores. It did not cause cognitive and motor deterioration. These results might possibly be due to small sample size.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Social Behavior Disorders; Treatment Outcome

Acute agitation is a common presentation in emergency departments and is often secondary to an underlying psychotic condition. The aim of this study was to compare the effectiveness of three second generation antipsychotics (risperidone, olanzapine, quetiapine) versus haloperidol in the treatment of psychotic agitation for up to 72 h.. We recruited 101 patients with acute psychosis who were admitted at the Mental Health Department 1 South of Turin, Psychiatric Emergency Service of San Giovanni Battista Hospital, from June 2004 to June 2005.. Aggressive behavior, as measured by Modified Overt Aggression Scale and Hostility-suspiciousness factor derived from the Brief Psychiatric Rating Scale, significantly improved in all groups, with no significant between-group differences. Extrapyramidal symptoms were more common in haloperidol treated patients compared with patients receiving risperidone, olanzapine or quetiapine.. Our results show that in the clinical practice setting of emergency psychiatry olanzapine, risperidone, quetiapine are as effective as haloperidol and better tolerated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Haloperidol; Hostility; Humans; Italy; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This study evaluated the effect of switching to quetiapine vs. risperidone continuation on sexual functioning in outpatients with risperidone-associated sexual dysfunction. Outpatients (n=42, age>or=18 years) with schizophrenia or schizoaffective disorder who experienced risperidone-associated sexual dysfunction were randomized to 6 weeks of double-blind risperidone continuation (mean dose=4.1 mg/day, S.D.=1.2) or quetiapine switch (mean dose=290.0 mg/day, S.D.=55.2) treatment. The five-item Arizona Sexual Experience Scale (ASEX) assessed sexual functioning at baseline and subsequently at weeks 2, 4 and 6. A mixed-model analysis of repeated measures included gender and baseline ASEX and PANSS scores as covariates. There was no significant Treatment Group effect for ASEX total scores and ASEX sub-items, and no significant Treatment GroupxPeriod interaction for ASEX total scores and ASEX sub-items. Treatment Group effects were not significantly different in any of the prospective weeks for ASEX total scores and ASEX sub-items. Adjusted mean ASEX total scores were slightly lower in the quetiapine switch group than in the risperidone continuation group at weeks 2 and 6 (21.27 vs. 22.18 and 18.51 vs. 20.53, respectively), but were nearly identical at week 4 (20.01 vs. 20.15). In this pilot trial, sexual functioning did not differ significantly between outpatients receiving quetiapine switch vs. risperidone continuation, although the quetiapine switch group had slightly lower adjusted mean ASEX total scores at weeks 2 and 6.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Sexual Behavior; Sexual Dysfunctions, Psychological

To evaluate predictors of treatment discontinuation against medical advice and poor medication adherence among first-episode patients treated with olanzapine, quetiapine, or risperidone.. First-episode patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder (DSM-IV) were randomly assigned to olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) as part of a 52-week, randomized, double-blind, flexible-dose, multicenter study. Patients were enrolled from 2002 to 2004 at one of 26 sites in the United States and Canada. Survival analysis tested for predictors of treatment discontinuation against medical advice, while mixed models tested for predictors of poor medication adherence. Significant findings from the final models were replicated in sensitivity analyses.. Of the 400 patients randomly assigned to treatment, 115 patients who discontinued treatment against medical advice and 119 study completers were compared in this analysis. Poor treatment response (p < .001) and low medication adherence (p = .02) were independent predictors of discontinuation against medical advice. Ongoing substance abuse, ongoing depression, and treatment response failure significantly predicted poor medication adherence (p < .01). Higher cognitive performance at baseline and ethnicity (black) were also associated with lower medication adherence (p < .05). An association between poor medication adherence and illness insight at study entry was found at trend level (p = .059).. This study highlights the importance of treatment response in predicting discontinuation against medical advice and poor adherence to medication in first-episode patients. These results also support interventions to improve adherence behavior, particularly by targeting substance use disorders and depressive symptoms.. ClinicalTrials.gov identifier NCT00034892 (http://www.clinicaltrials.gov).

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Culture; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Surveys and Questionnaires; Treatment Refusal

Patients with combat-related post-traumatic stress disorder (PTSD) with psychotic features frequently fail to respond to antidepressants. Previous research has shown that these patients improve significantly after monotherapy with two atypical antipsychotics, olanzapine and risperidone. This study investigated the clinical outcome of another atypical antipsychotic, quetiapine, in war veterans with combat-related PTSD with psychotic features. Male war veterans (n=53) with DSM-IV-diagnosed PTSD with psychotic symptoms completed 8 wk of in-patient treatment with quetiapine (25-400 mg/d). The reductions in the total and subscale scores on the Clinician-Administered PTSD Scale (CAPS), and the increase in the Clinical Global Impression - Improvement Scale (CGI-I) were the primary outcome measures, and reductions in the Positive and Negative Syndrome Scale (PANSS) were the secondary outcome measures. The CGI - Severity of Illness scale (CGI-S) was used to assess the global clinical improvement. Drug-Induced Extrapyramidal Symptoms scale recorded adverse effects. Two, 6 and 8 wk treatment with quetiapine significantly reduced total and the subscales scores on the CAPS, PANSS, and CGI-S scales, in patients with psychotic PTSD. The results indicate that 8 wk of monotherapy with quetiapine reduced the majority of the psychotic and PTSD symptoms in the patients. Our present and previous data suggest that treatment-resistant psychotic PTSD patients may improve after taking atypical antipsychotics.

Topics: Adolescent; Adult; Antipsychotic Agents; Combat Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Stress Disorders, Post-Traumatic

This double-blind randomized study examined the effect of quetiapine (QTP) on drug-induced psychosis (DIP) in Parkinson's disease (PD). Conventional antipsychotic drugs are associated with adverse extrapyramidal effects. QTP is a new atypical antipsychotic drug used in the treatment of psychosis in PD. A total of 58 consecutive psychotic PD patients (mean age, 75 +/- 8.3 years; mean disease duration, 10.5 +/- 6.4 years; 29 with dementia) were randomly assigned to 2 groups: 30 were treated with QTP (mean dose, 119.2 +/- 56.4 mg) and 28 received placebo for 3 months. The motor part of the Unified Parkinson's Disease Rating Scale, the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, the Hamilton Rating Scale for Depression, the Epworth Sleepiness Score, and the Clinical Global Impression Scale were administered before and during the study. No significant difference was found between the groups in all parameters. There were 32 PD patients (55%) completed the 3-month study (15 [26%] QTP and 17 [29%] placebo). Treatment was interrupted in 15 patients in the QTP and 11 in the placebo groups. This double-blind study did not show a beneficial effect of QTP for the treatment of DIP in PD. The high rate of withdrawal probably influenced the results. Larger double-blind studies are required.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index

There are developmental and age-dependent differences in the pharmacokinetics and the pharmacodynamics of drugs in children and adolescents. Therefore, there is a need to carry out standardised studies to find out therapeutic ranges of plasma/serum concentrations in psychopharmacotherapy of children and adolescents. The aim of this prospective study was to examine the relationship between quetiapine serum concentration, treatment response, and side effects in a clinical setting to elucidate the age-specific therapeutic range of quetiapine in adolescents.. Over a period of two years, therapeutic drug monitoring (TDM) was routinely performed in 21 adolescents (mean age was 15.9+/-1.5 years, 57% male) with psychotic disorders according to the guidelines of the AGNP TDM expert group. The psychopathology was assessed by using the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS). Side effects were assessed by using the Dose Record and Treatment Emergent Symptom Scale (DOTES). Trough quetiapine concentrations were determined under steady state conditions after multiple-dose regimes (median 600 mg/day; range 100-800 mg/day).. There was a marked variability of the serum concentrations, ranging from 19-877 ng/ml. 40.8% of the determined values were below and 24.5% above the therapeutic range (70-170 ng/ml) recommended for adults. None of the patients had severe side effects. We found a weak correlation between dose and serum concentration of quetiapine and no relationship between serum concentration and treatment response.. There are several limitations of this study, and our results should therefore be interpreted with caution. Notwithstanding, differences in the ontogenesis of pharmacokinetics and pharmacodynamics may be the reason for the difference in the relationship between blood concentrations and therapeutic response to psychopharmaca in children, adolescents and adults. Further studies using larger samples, baseline assessment of psychopathology, definition of the treatment interval and investigation of clinically relevant interactions with various co-medications are warranted to improve the limitations of this pilot study.

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Pilot Projects; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism.. Multicenter randomized, double-blind, placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies (n = 23), Parkinson disease (PD) with dementia (n = 9), or Alzheimer disease with parkinsonian features (n = 8). The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale (BPRS) from baseline to 10 weeks of therapy. For tolerability it was change in the Unified PD Rating Scale (UPDRS) motor section over the same time period. The trial was confounded by the need for a design change and incomplete recruitment.. No significant differences in the primary or secondary outcome measures of efficacy were observed. An unexpectedly large placebo effect, inadequate dosage (mean 120 mg/day), and inadequate power may have contributed to lack of demonstrable benefit. Quetiapine was generally well-tolerated and did not worsen parkinsonism, but was associated with a trend toward a decline on a measure of daily functioning.. Quetiapine was well-tolerated and did not worsen parkinsonism. Although conclusions about efficacy may be limited, the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism. These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antiparkinson Agents; Antipsychotic Agents; Cholinesterase Inhibitors; Confounding Factors, Epidemiologic; Dementia; Dibenzothiazepines; Donepezil; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indans; Lewy Body Disease; Male; Neuropsychological Tests; Parkinson Disease; Patient Selection; Piperidines; Placebo Effect; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Research Design; Severity of Illness Index; Treatment Failure

Rapid resolution of symptoms is a priority for clinicians treating acute psychosis, and rapid initiation of pharmacotherapy may prove beneficial. This study examined rapid dose initiation of quetiapine in acutely ill patients.. A 2-week, multicentre, randomised, parallel-group, open study. Inpatients (n = 269) diagnosed with schizophrenia or schizoaffective disorder received rapid (n = 139) or conventional (n = 130) initiation of quetiapine, followed by flexible dosing (maximum 800 mg/day). Primary outcome included proportion of patients experiencing > or =1 episode of selected AEs (somnolence, dizziness, orthostatic hypotension) during Week 1. Secondary outcomes included discontinuations due to AEs, and efficacy assessed by BPRS and CGI-S scores.. The proportion of patients with > or =1 selected AE during Week 1 was 5.4% and 10.1% in the conventional and rapid initiation groups, respectively. Most common AEs (>5% patients) were hypotension, tachycardia, somnolence and sedation. Overall, four (3.1%) and three (2.1%) patients from the conventional and rapid initiation group, respectively, withdrew due to AEs. BPRS and CGI-S scores decreased significantly (p < 0.001) from baseline in both groups.. A higher proportion of patients experienced AEs with rapid initiation of quetiapine (800 mg/day by Day 4), although withdrawals due to AEs were comparable. Rapid initiation of quetiapine was generally well tolerated and effective in this setting.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.. Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.. A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).. Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Dropouts; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sleep Stages; Sleep Wake Disorders; Treatment Outcome; Weight Gain

The authors sought to compare the effects of olanzapine, quetiapine, and risperidone on neurocognitive function in patients with early psychosis.. In a 52-week double-blind, multicenter study, 400 patients early in the course of psychotic illness (<5 years) were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day). The mean modal daily dose was 11.7 mg (SD=5.3) for olanzapine, 506 mg (SD=215) for quetiapine, and 2.4 mg (SD=1.0) for risperidone. A total of 224 patients completed neurocognitive assessments at baseline and at 12 weeks, and 81 patients also completed them at 52 weeks. Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and from the Brief Assessment of Cognition in Schizophrenia.. At week 12, there was significant improvement in neurocognition for each treatment (p<0.01), but no significant overall difference between treatments. Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine, 0.33 for quetiapine, and 0.32 for risperidone. Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine, 0.34 for quetiapine, and 0.22 for risperidone. Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52.. Olanzapine, quetiapine, and risperidone all produced significant improvements in neurocognition in early-psychosis patients. Although cognitive improvements were modest, their clinical importance was suggested by relationships with improvements in functional outcome.

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Least-Squares Analysis; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Treatment Outcome

The use of adjunctive psychotropics and the costs of polypharmacy in patients randomized to receive risperidone or quetiapine were compared in a placebo-controlled double-blind study conducted in India, Romania, and the United States.. The efficacy and safety of risperidone, quetiapine, and placebo were compared in a 14-day monotherapy phase in patients experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder. This was followed by a 28-day, additive-therapy phase during which addition of antipsychotics or other psychotropic medications was permitted. Risperidone was received by 153 patients in the monotherapy phase and 133 in the additive therapy phase, quetiapine by 156 and 122, respectively, and placebo by 73 and 53. Rates of polypharmacy were examined using the Cochran-Mantel-Haenszel, Kaplan-Meier, and Cox regression methods. Costs of polypharmacy were analyzed by non-parametric Wilcoxon 2-sample tests.. Primary study results have been reported elsewhere (Potkin et al., Schizophr Res 2006;85:254-65). Mean (+/-SD) doses at the additive-therapy baseline were 4.7 +/- 0.9 mg/day of risperidone and 579.0 +/- 128.9 mg/day of quetiapine. Additional psychotropics were received by 36% of the risperidone group, 58% of the quetiapine group (p < 0.01), and by 58% of the placebo group. Antipsychotics accounted for > 95% of the added psychotropics, the most common being olanzapine and haloperidol. The relative risk (quetiapine vs. risperidone) for antipsychotic polypharmacy was 1.90 (p = 0.001; 95% CI 1.29, 2.80). The mean projected cost of additional antipsychotics per randomized patient during the additive-therapy phase was $57.03 in the risperidone group and $101.64 in the quetiapine group (p < 0.01).. The results confirm earlier reports of higher rates of polypharmacy with quetiapine than with risperidone. The findings also reveal substantial between-treatment differences in costs associated with polypharmacy. Limitations of the study include that the study was of short duration and that a high proportion of patients were recruited from countries other than the United States.

Topics: Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Humans; Placebos; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

The first episode of a psychotic disorder provides a unique opportunity to initiate optimal treatment but when a new medication becomes available, little data exist to guide the appropriate use in this population.. The objectives were to determine the optimal doses and titration of quetiapine for this group and to measure outcomes (including symptom response, social functioning, mood alterations, motor symptoms, metabolic parameters and cognitive functioning) over 2 years of treatment with quetiapine.. Thirty nine subjects with a first episode of psychosis referred to the Nova Scotia Early Psychosis Program in Halifax, Canada, were invited to participate in this study. Standardized clinical, laboratory, and neuropsychological assessments were performed at baseline and following treatment with quetiapine at intervals out to 2 years.. Quetiapine was effective in treating the psychotic and mood symptoms while not causing extra-pyramidal signs or symptoms (EPSS). Pre-existing motor dysfunction improved. No anticholinergic medications were required. Several domains of cognitive function also improved (sustained attention, the number of perseverative errors, visuomotor speed and sequencing, verbal fluency and verbal memory). Weight gain was observed along with increases in cholesterol levels but there was no glucose dysregulation.. The results of this two year, naturalistic study of people with a first episode of psychosis indicated that quetiapine was well tolerated and effective for this population. Significant improvements in cognitive functioning also provided evidence for potential longer-term benefits of early and optimal treatment with this agent. However, monitoring metabolic parameters, as recommended for other atypicals, is likely prudent.

Topics: Adolescent; Adult; Antipsychotic Agents; Demography; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Psychomotor Disorders; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Socioeconomic Factors; Treatment Outcome

To determine how the use of the newer, so called atypical antipsychotic medications, effects the pharmacoeconomic treatment burden of schizophrenia and related conditions and to provide a clear comparison of the costs and risks associated with these atypical drugs.. In this 2-year, open-label, prospective study, resource utilization (RU) data were collected on 160 patients with these conditions. A comparison between risks and costs was performed by combining the generalized CNOMSS data on both economic factors and risk assessments.. The main findings of the study were that the total adjusted 1- and 2-year costs were lowest for quetiapine. Drug acquisition costs were lowest for risperidone for both the 1- and 2-year cohorts. Clozapine use was predictably associated with the highest overall and medication costs at both 1 and 2 years.. Treatment with risperidone or quetiapine was associated with the lowest overall costs when compared with olanzapine or clozapine.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Canada; Clozapine; Cohort Studies; Cost of Illness; Cost-Benefit Analysis; Dibenzothiazepines; Drug Costs; Female; Health Care Surveys; Health Resources; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia

The goal of this pilot study was primarily to explore the safety and, secondarily, the efficacy of the use of "prn" quetiapine for treatment of moderate agitation accompanied by psychosis in an emergency department setting.. This was an open-label study in which 20 patients with psychotic agitation were treated in the emergency department with 100, 150, or 200 mg of quetiapine. Physicians who were unaffiliated with the study established the diagnoses and selected the doses to be used for each patient. A rater who was blinded to the dose performed the assessments. The primary safety measure was the onset of orthostatic hypotension. The primary efficacy measure was a 40% reduction in scores on the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) over 120 minutes. The secondary efficacy measure was a reduction of 2 points or more on the Behavioral Activity Rating Scale (BARS) at 120 minutes post-dose. All subjects provided written informed consent.. With regard to safety outcomes, 40% of subjects exhibited orthostasis by 120 minutes, although only 25% of these patients described clinically significant symptoms. In terms of efficacy, 50% of subjects experienced at least a 40% reduction in PANSS-EC scores at 2 hours, while 68.8% showed reductions of 2 points or more in scores on the BARS over the same time period.. Quetiapine demonstrated some efficacy as a sedative agent in the emergency setting, although no clear dose-response pattern emerged over the narrow dose range tested. Orthostasis was common and did not correlate with dosing. This small study did not support the use of quetiapine to treat acute agitation in potentially volume-depleted patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Comorbidity; Dibenzothiazepines; Dose-Response Relationship, Drug; Emergency Medical Services; Female; Hospitalization; Humans; Hypotension, Orthostatic; Male; Middle Aged; Pilot Projects; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Time Factors

The objectives of this study were to evaluate the efficacy, safety, and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning.. The authors conducted a multicenter, double-blind, placebo-controlled, randomized trial of flexibly dosed quetiapine and haloperidol. Primary outcomes were change in total Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness (CGI-S) scores at week 10. Secondary outcomes included BPRS factors, Neuropsychiatric Inventory (NPI), Multidimensional Observation Scale for Elderly Subjects (MOSES), and Physical Self-Maintenance Scale (PSMS).. Two hundred eighty-four participants (mean age: 83.2 years) were randomized; 63.4% completed; and mean Mini-Mental State Examination score was 12.8. Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol. No differential benefit was seen on any psychosis measure. BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol. BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo. No NPI factors showed change, including the agitation factor. MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine. Somnolence occurred in 25.3%, 36.2%, and 4.1% of the quetiapine, haloperidol, and placebo groups, respectively; parkinsonism was most prevalent in the haloperidol group; other safety and tolerability measures differed little among groups.. All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed. Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation. Tolerability was better with quetiapine compared with haloperidol.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Brain; Brief Psychiatric Rating Scale; Cholinesterase Inhibitors; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease, Secondary; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Substance Withdrawal Syndrome

This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Research Design; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Social Adjustment; Treatment Outcome

Magnetic resonance imaging (MRI) studies measuring basal ganglia volumes in first episode patients suggest that treatment with typical neuroleptics leads to alteration in these brain structures. However, caudate nuclei volumes (CNV) of untreated first-episode patients may even be smaller than in healthy controls. We investigated whether CNV of newly diagnosed neuroleptic-naive psychotic patients differ as compared to an age- and sex-matched healthy control group to detect possible treatment effects early in the course of this illness. Magnetic resonance images were acquired in 37 un-medicated psychotic patients and 37 healthy controls. Ten of the patients were re-examined after 12 weeks of treatment with the second generation antipsychotic quetiapine. Regions of interest (ROI) delineating the caudate nuclei bilaterally were drawn manually using Brain Image software. The neuroleptic-naive patients showed a mean CNV of 8.40 cc (SD=1.01) and the controls of 8.55 cc (SD=1.16). There was no significant difference between groups (F=.600; P=.441). In contrast to previous studies in patients treated with typical neuroleptics, this cross-sectional MRI study did not find significant differences in CNV of neuroleptic-naive first-episode patients compared to healthy controls.

Topics: Adult; Antipsychotic Agents; Case-Control Studies; Caudate Nucleus; Dibenzothiazepines; Female; Humans; Magnetic Resonance Imaging; Male; Psychotic Disorders; Quetiapine Fumarate

To compare the long-term efficacy and tolerability of oral quetiapine with those of intramuscular haloperidol.. Patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder requiring long-term antipsychotic treatment were randomly assigned to open-label oral quetiapine or intramuscular haloperidol decanoate for 48 weeks. Clinicians were instructed to target dosing at 500 mg/day of quetiapine or 200 mg of haloperidol decanoate every 4 weeks. The Positive and Negative Syndrome Scale was used to assess efficacy; the Simpson-Angus Scale and the Barnes Akathisia Scale were used to assess safety and tolerability. For statistical analyses, a general linear mixed-model repeated-measures analysis of covariance was used, with change scores for dependent variables computed with the baseline score as covariate. Data were collected from 1998 to 2001.. Thirty-five patients were enrolled, but 6 did not participate after being informed of their treatment assignment; 4 of the 6 withdrawals were assigned to haloperidol decanoate. Mean doses at week 48 were 493 mg/day of quetiapine (N = 16) and 170 mg/28 days of haloperidol decanoate (N = 9). Survival analysis showed no between-group differences in estimates of the number of patients remaining exacerbation-free over time. Both drugs were efficacious, but quetiapine was significantly better than haloperidol decanoate in controlling negative symptoms (p < .05). The incidence of extrapyramidal symptoms was low in both groups; patients receiving quetiapine showed significantly greater improvement in rigidity and akathisia (p < .05).. Oral quetiapine was as efficacious as intramuscular haloperidol in preventing symptom exacerbation over 48 weeks in patients with schizophrenia or schizoaffective disorder, with fewer extrapyramidal symptoms, especially rigidity and akathisia. Quetiapine was more efficacious than haloperidol decanoate in treating negative symptoms.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Haloperidol; Humans; Incidence; Injections, Intramuscular; Long-Term Care; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Survival Analysis; Treatment Outcome

To compare sexual functioning in patients treated with quetiapine or risperidone.. This open-label study included patients with schizophrenia or a related psychotic illness who were randomized to quetiapine (200-1200 mg/d) or risperidone (1-6 mg/d) for 6 weeks. Sexual dysfunction was assessed by a semistructured interview, the Antipsychotics and Sexual Functioning Questionnaire (ASFQ), based upon the Utvalg for Kliniske Undersogelser (UKU).. Four of 25 quetiapine-treated patients (16%) and 12 of 24 risperidone-treated patients (50%) reported sexual dysfunction (chi 2 = 6.4; df = 1; P = 0.006) on the ASFQ. Six patients (11.7%; 4 on risperidone, 2 on quetiapine) spontaneously reported sexual dysfunction. The mean+/-SD dose was 580+/-224 mg/d for quetiapine and 3.2 +/- 1.3 mg/d for risperidone. Mean +/- SD prolactin levels in quetiapine- and risperidone-treated patients were 13.8 +/- 17.9 and 57.7 +/- 39.7 ng/mL, respectively.. Sexual dysfunction was less common in patients treated with quetiapine than with risperidone. Direct questioning about sexual functioning is necessary to avoid underestimating the frequency of sexual side effects in patients with schizophrenia and related psychotic disorders.

Topics: Adolescent; Adult; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Surveys and Questionnaires; Testosterone; Treatment Outcome

While the atypical antipsychotics should ultimately reduce the prevalence of tardive dyskinesia, it is likely to remain a significant clinical problem for a long time to come. No strategy has clearly emerged as the treatment of choice for tardive dyskinesia. Atypical antipsychotics have reduced propensities for producing acute extrapyramidal symptoms (EPS) and possibly tardive dyskinesia and may be effective in treating patients with established tardive dyskinesia.. This 12-month, randomized, investigator-blinded study compared the efficacy of quetiapine (N = 22) and haloperidol (N = 23) in treating patients with DSM-IV schizophrenia or schizoaffective disorder and established tardive dyskinesia. Dyskinesia was assessed using the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale scores and the Clinical Global Impression (CGI) dyskinesia scores. Other EPS, weight, serum prolactin level, and glycosylated hemoglobin level were also assessed. Subjects were enrolled in the study between April 2000 and March 2002.. Mean endpoint doses were 400 mg/day of quetiapine and 8.5 mg/day of haloperidol. Compared with the haloperidol group, the quetiapine group showed significantly greater improvements in ESRS dyskinesia (6 and 9 months [p or= 50% symptom reduction) was greater with quetiapine than haloperidol (64% [9/14] and 37% [6/16] at 6 months; 55% [6/11] and 28% [4/14] at 12 months). Other EPS decreased significantly with quetiapine at 3 (p =.01), 6 (p =.01), and 9 (p =.002) months. Serum prolactin levels decreased with quetiapine but increased with haloperidol, differing significantly between the groups at endpoint (p =.005). No significant changes in weight or glucose metabolism were recorded in either group.. Quetiapine effectively reduces the severity of tardive dyskinesia and is well tolerated in patients with established tardive dyskinesia.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Single-Blind Method; Treatment Outcome

To compare the tolerability of quetiapine with risperidone in older outpatients.. Post hoc analysis of a subset of older patients (aged 60-80; n = 92) from a randomized, 4-month, multicenter, open-label trial comparing quetiapine and risperidone in an outpatient setting. Participants had various neuropsychiatric disorders associated with psychosis as defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th edn).. The main outcome measure was an extrapyramidal symptoms (EPS) checklist, used to assess motor symptoms, including parkinsonism, at baseline and after treatment. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale were used to assess therapeutic efficacy.. Substantial EPS (defined as EPS requiring a dosage adjustment or use of medication to reduce EPS) occurred less often with quetiapine (median dosage, 200 mg/day) than with risperidone (median dosage, 3 mg/day); odds ratio, 0.31 (P < 0.03). Quetiapine was also less likely than risperidone to cause akathisia or hypertonia. Both compounds produced comparable reductions in PANSS scores.. Interpretation of findings in this report is limited by the open-label design of the study and the post hoc nature of this analysis. However, the results suggest that quetiapine, when given within the recommended dosage range, has a benign EPS profile, with potentially greater tolerability and comparable efficacy to risperidone in older outpatients with psychotic disorders.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Risperidone

To evaluate the efficacy and safety of administering quetiapine once vs twice daily.. Utilizing a double-blind design, 21 hospitalized adult men or women with DSM-IV schizophrenia or schizoaffective disorder, who had received unchanged doses (for 2 weeks) of either 400 or 600 mg daily of quetiapine administered in 2 doses, were randomly assigned to once- or twice-daily administration for 4 weeks and then crossed over to the opposite dosing regimen for an additional 4 weeks. Standard psychopathology and safety measures were used in the study.. Nearly 70% (15/21) of the subjects met the a priori efficacy responder criteria with no statistical differences in response between those assigned to once- or twice-daily quetiapine administration. Statistical analyses confirmed that most subjects maintained efficacy during the switch to once- or twice-daily administration with quetiapine. A minority (15%) did experience worsening of symptoms or orthostatic hypotension during the crossover. Quetiapine was generally well tolerated at either twice- or once-daily administration.. These pilot data suggest that it is clinically feasible to switch most quetiapine-treated subjects receiving a therapeutic twice-daily dosing schedule to a once-daily regimen. A minority may experience worsening of symptoms or orthostatic hypotension during the switch. This strategy of administering quetiapine entirely at bedtime may promote improved adherence to treatment.

Topics: Adolescent; Adult; Aged; Anticarcinogenic Agents; Antipsychotic Agents; Cross-Over Studies; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Fumarates; Humans; Male; Middle Aged; Pilot Projects; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Quetiapine is a novel, atypical antipsychotic agent that has been shown to provide long-term efficacy without serious adverse effects in adults. This is the first study of the extended use of quetiapine in adolescents. Five boys and 5 girls, ages 12.3 to 15.9 years, with diagnoses of schizoaffective disorder (n = 7) or bipolar disorder with psychotic features (n = 3) were eligible for entry into this single-site, 88-week, open-label trial. Subjects had completed a pharmacokinetic study over 23 days, during which the dosage of quetiapine was increased sequentially from 25 mg bid to a maximum of 400 mg bid (800 mg/day) (McConville et al. 2000). In the open-label extension of this trial, which followed directly after this trial, a physician's choice design allowed for flexible dose titration of quetiapine by the study physician to an optimal dose for each patient, with ending doses ranging from 300 mg/day to 800 mg/day. Concomitant medications, especially for anxiety and/or manic symptoms, were allowed as deemed necessary. Tolerability and safety were assessed using clinical laboratory tests, physical examinations, measurements of vital signs, interviews for selective symptomatology, and electrocardiograms. Psychiatric measurements included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and the modified Scale for the Assessment of Negative Symptoms (SANS). Neurologic symptom ratings included the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Mean BPRS, CGI, and SANS scores improved significantly during the trial (p < 0.05). No extrapyramidal symptoms or evidence of tardive dyskinesia was seen. Clinically, there was a nonsignificant increase in mean weight and body mass index at week 64. This long-term study suggests that quetiapine is a well-tolerated antipsychotic agent that is efficacious for the treatment of symptoms of selected psychotic disorders in adolescents.

Topics: Adolescent; Adolescent Psychiatry; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Time Factors; Treatment Outcome

In the present naturalistic study, the effectiveness and safety of quetiapine, risperidone and olanzapine were compared in the treatment of non selected acutely psychotic patients. It was observed that the rate of antipsychotic switch because of a lack of efficacy or side effects was higher in the quetiapine treated cases in comparison with the risperidone or olanzapine treated cases. The proportion of cases concomitantly treated with typical neuroleptics was significantly higher in the quetiapine group compared with the other two groups. In the outcome of non crossover cases, there were more improvements in the risperidone and olanzapine groups than in the quetiapine group. The results of this study suggest that quetiapine is not as efficacious as risperidone or olanzapine in the emergency psychiatric setting. Due to the methodological limitations of the study, these results must be considered preliminary and need confirmation.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Sampling Studies; Treatment Outcome

A 3-year open-label study was conducted to determine the long-term safety and efficacy of quetiapine monotherapy in schizophrenia and schizoaffective disorder.Twenty-three male outpatients previously stable but with inter-episode residual symptoms on classical antipsychotics and/or risperidone and who had complained of side effects were selected. To initiate quetiapine, patients were hospitalized for 13 days and then treated as outpatients. Quetiapine dosage was adjusted according to therapeutic effects. Only five patients (21.7%) completed 77 to 96 weeks of the study. Initial dose was 261 +/- 65.6 mg/day (mean +/- S.D.) administered in divided doses, with an ending dose of 487 +/- 209.6 mg/day, corresponding with an 86.6% dose increase over the course of the study. For those completing 12 weeks or less (n = 11), mean ending dose was 362 +/- 184.8 mg/day a 38.7% dose increase over baseline. For those completing 25 weeks or more (n = 12), mean ending dose was 592 +/- 178.2 mg/day, a 126.8% dose increase over baseline. Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met criteria for supersensitivity psychosis (SSP).Therapeutic tolerance and rebound psychosis were found to develop with quetiapine in male patients with a history of chronic treatment with classical antipsychotics. Seeman and Tallerico3 have proposed pharmacologic explanations for quetiapine and clozapine drug-induced rebound phenomena.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Tolerance; Humans; Longitudinal Studies; Male; Middle Aged; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Schizophrenia

We examined the long-term consequences of switching patients from conventional to novel antipsychotic drugs, from a patient's perspective.. In a prospective, single-blinded, naturalistic study, a cohort of subjects (n=150) with schizophrenia or schizo-affective disorder (DSM-IV) were switched from conventional neuroleptic drugs to either risperidone (n=50), olanzepine (n=50) or quetiapine (n=50), and monitored for a period of 2 to 6 years. The ensuing natural history of transitions in treatments was charted, and the outcomes including symptoms, side effects, subjective tolerability of drugs and their impact on quality of life were documented with standardized rating scales.. Majority (85%) of the subjects benefited from a switch to the novel antipsychotic drugs, though some preferred to return to their original neuroleptic (8%), and others eventually required clozapine (7%) therapy. Novel antipsychotic drugs were significantly tolerated better, and had a positive impact on treatment-adherence, psychosocial functioning and quality of life. Among the novel drugs, risperidone was significantly better in improving negative symptoms, while olanzepine was particularly well tolerated and effective against comorbid anxiety and depressive symptoms. Patients treated with quetiapine reported fewer side effects, and showed a significantly greater improvement in neurocognitive deficits.. Novel antipsychotics emerged as the drug of choice in view of their overall effectiveness, though conventional neuroleptics and clozapine will continue to have a limited but distinct role in the management of schizophrenia. The challenge for clinicians lies in matching a patient's clinical and biochemical profile with that of a drug's pharmacological actions, in order to achieve optimum outcomes.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Multivariate Analysis; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Single-Blind Method

The aim of this study was to assess the effect of oral quetiapine on the steady-state pharmacokinetics of lithium.. This was an open-label trial in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who had demonstrated tolerability to combination lithium/ antipsychotic therapy. Patients received lithium for at least 1 week before screening and throughout the 18-day trial. Quetiapine was coadministered in fixed, stepwise, increasing doses of 25 to 250 mg TID on days 4 through 11, and maintained at 250 mg TID on days 12 through 14. Blood samples were drawn to monitor plasma concentrations of lithium and quetiapine. Psychiatric assessments included the Brief Psychiatric Rating Scale, the Clinical Global Impression severity of illness item, and the modified Scale for the Assessment of Negative Symptoms. Neurologic function was assessed using the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Other assessments included clinical laboratory testing, electrocardiography, physical examinations, and monitoring for spontaneously reported adverse events.. Nine men and 1 woman (mean [SE] age, 32.8 [1.9] years; mean [SE] body weight, 87.6 [3.3] kg) entered and completed the 18-day trial. Eight patients had bipolar disorder, 1 had paranoid schizophrenia, and 1 had schizoaffective disorder. Morning trough concentrations of lithium in serum (days 2, 6, 8, 10, 12, 14, and 17), as well as quetiapine and 2 of its metabolites in plasma (days 12, 13, and 14), did not appear to vary noticeably. Small increases were observed in the mean values of the area under the 12-hour serum lithium concentration-time curve and the maximum and minimum observed serum lithium concentrations when quetiapine was added to the lithium regimen. However, the increases were not considered clinically relevant by the investigators and were not statistically significant. A total of 91 adverse events were reported, 67 (73.6%) of which were not attributed to trial treatment. The most commonly reported adverse events during coadministration of lithium and quetiapine were somnolence (90.0% [9/10]), asthenia (70.0% [7/10]), dry mouth (30.0% [3/10]), nausea (30.0% [3/10]), vomiting (30.0% [3/10]), dizziness (30.0% [3/10]), tremor (30.0% [3/10]), and insomnia (20.0% [2/10]). There were no serious adverse events.. Measures of lithium and quetiapine concentrations did not vary significantly during combination therapy. Coadministered lithium and quetiapine were well tolerated in the patients studied.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Female; Humans; Lithium; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

The treatment of psychotic symptoms in patients with mood disorders is a complex challenge. Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms (EPS), worsening of depression, and functional impairment. Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS. The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in outpatients with psychosis.. In this 4-month, multicenter, open-label trial, patients were randomly assigned in a 3:1 ratio of quetiapine to risperidone, and both drugs were flexibly dosed. Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses, including schizoaffective disorder, bipolar I disorder, major depressive disorder, delusional disorder, Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance abuse dementia. Patients were classified as mood disordered if they had bipolar disorder, major depressive disorder, or schizoaffective disorder. Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale. The Hamilton Rating Scale for Depression (HAM-D) was used to assess the level of depressive symptoms. The primary tolerability assessment was presence or absence of substantial EPS, defined as EPS severe enough to require an alteration in treatment.. A total of 554 patients were randomly assigned to quetiapine and 175 to risperidone. Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone. Although both agents produced improvements in mean HAM-D scores, quetiapine produced a greater improvement than risperidone in all patients (p =.0015). Within the mood-diagnosed population, incidences of both substantial EPS (p =.001) and at least moderate EPS (p =.0373) occurred significantly less frequently among patients taking quetiapine. For patients with non-mood diagnoses, incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone (p =.062); however, this was not statistically significant.. These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis.

Topics: Ambulatory Care; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Risperidone

The effects of haloperidol, risperidone, and thioridazine on the pharmacokinetics and side-effect profile of quetiapine were investigated in 36 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a single-center, two-period, multiple-dose, open-label, randomized trial. Over a one-to two-week period, quetiapine doses were escalated to 300 mg twice daily (bid). Patients were then treated for at least 7 days at the target quetiapine dose and subsequently entered into the combination therapy period, receiving haloperidol (7.5 mg, bid), risperidone (3 mg, bid), or thioridazine (200 mg, bid) for 8.5 days (after 3 days of dose escalation). Key assessments included the pharmacokinetics of quetiapine at steady state (area under the curve within a dosing interval [AUCtSS], maximum [CmaxSS], and minimum [CminSS] observed plasma concentrations, and oral clearance [Cl/f]), as well as the UKU Side Effect Rating Scale scores and safety evaluations. Neither risperidone nor haloperidol had significant effects on quetiapine pharmacokinetics. However, thioridazine produced statistically significant changes, decreasing the least squares means values of the AUCtSS, CmaxSS, and CminSS by 40%, 47%, and 31%, respectively, and increasing Cl/f by 68%. Increases in the following adverse events were noted during coadministration: somnolence (risperidone), insomnia and dry mouth (all three coadministered therapies), and dizziness (thioridazine). UKU side effect items that became worse in >or= 25% of patients during each coadministration period included sedation and increased sleep duration. Results of laboratory tests, electrocardiograms, and vital sign measurements revealed few clinically important changes. Clinical stability can be maintained with good tolerability during the transition from quetiapine monotherapy to periods of coadministration with haloperidol, risperidone, or thioridazine. Coadministration of either haloperidol or risperidone did not have any important effects on the steady-state pharmacokinetics of quetiapine. Thioridazine significantly increased the oral clearance of quetiapine. Increased doses of quetiapine may be necessary to control psychotic symptoms when thioridazine is coadministered with quetiapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Metabolic Clearance Rate; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thioridazine

The effects of fluoxetine and imipramine on the pharmacokinetics and nonpsychiatric side effect profile of quetiapine fumarate were investigated in 26 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a multicenter, two-period, multiple-dose, open-label, randomized trial. Over a 1- to 2-week period, patients were titrated to a 300-mg twice-daily dose of quetiapine. Patients treated for at least 7 days at the target dose entered a combination therapy period, receiving fluoxetine (60 mg daily) or imipramine (75 mg twice daily) for 8 days. Key assessments included pharmacokinetic analysis of quetiapine, the Udvalg for kliniske undersøgelser (UKU) Side Effect Rating Scale, and safety evaluations (e.g., adverse events, electrocardiograms, laboratory tests, and vital signs). Fluoxetine increased the quetiapine area under the plasma concentration time curve during a 12-hour interval (+12%), maximum plasma concentration during the dosing interval (C(ss)(max); +26%), and minimum plasma concentration at the end of the dosing interval (+8%), although it decreased oral clearance (-11%). The change in C(ss)(max) was statistically although not clinically significant. Imipramine did not affect the pharmacokinetics of quetiapine. Overall, scores on the UKU Side Effect Rating Scale improved during combination therapy with either agent, and no statistically significant deterioration was observed for any item. For safety assessments, the only clinically remarkable event was an imipramine-associated complete left bundle branch block in one patient. No unexpected side effects were reported. In conclusion, combination therapy with quetiapine and fluoxetine or imipramine had a minimal effect on quetiapine pharmacokinetics and was well tolerated.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Imipramine; Male; Metabolic Clearance Rate; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.

Topics: Adolescent; Adult; Analysis of Variance; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Humans; Male; Middle Aged; Phenytoin; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Cognition; Dibenzothiazepines; Humans; Male; Middle Aged; Psychological Tests; Psychotic Disorders; Quetiapine Fumarate

Use of antipsychotic medication intermittently or over the long term may be necessary in treating patients with bipolar disorder whose symptoms have responded suboptimally to standard mood-stabilizing agents. Quetiapine fumarate is an effective novel antipsychotic with mixed serotonergic (5-HT2) and dopaminergic (D2) activity. This is an open-label, 12-week prospective study to assess the efficacy and tolerability of quetiapine in the treatment of patients with bipolar and schizoaffective disorder who were suboptimally responsive to mood stabilizers alone.. Participants in the study were inpatients or outpatients with a DSM-IV diagnosis of bipolar or schizoaffective disorder. Baseline psychopathology was evaluated with the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), and the Hamilton Rating Scale for Depression (HAM-D). Involuntary movements were rated with the Simpson-Angus Neurologic Rating Scale. Quetiapine was added on an open-label basis and increased to optimum clinical dosage. Psychopathology and Abnormal Involuntary Movement Scale ratings were repeated weekly for the first 4 weeks and then again at weeks 8 and 12.. Ten individuals with bipolar disorder and 10 with schizoaffective disorder received quetiapine therapy. Overall, patients improved, with significant improvement in BPRS (p < .001), YMRS (p = .043), and HAM-D scores (p = .002). Simpson-Angus score also significantly decreased (p = .02). Overall. quetiapine was well tolerated by patients in this group with serious mood disorders. The mean +/- SD quetiapine dose was 202.9 +/- 124.3 mg/day (range, 50-400 mg/day). Mean weight gain was 10.9 lb (4.9 kg).. Although limited by its small size, open-label design, and relative gender homogeneity, this study suggests that quetiapine therapy may be useful in the treatment of individuals with serious mood disorders who are suboptimally responsive to mood stabilizers alone. These preliminary findings should be explored in larger, controlled trials.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Lithium; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Valproic Acid; Weight Gain

The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice.. The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms.. This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D).. A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028).. The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Outpatients; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology

To study the effectiveness, safety, and tolerability of quetiapine in adolescents with psychotic disorders.. This study was an 8-week, open trial using quetiapine with 15 adolescents, ages 13-17 years, mean age 15.1 years, with a diagnosis of a psychotic disorder. Our primary instruments focused on psychotic symptomatology as measured by the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Positive and Negative Syndrome Scale (PANSS), and the Young Mania Rating Scale (YMRS). Other measures included adverse events, clinical laboratory tests, vital signs, electrocardiogram (ECG), extrapyramidal (EPS) measures, and ophthalmologic examination.. Quetiapine significantly reduced psychotic symptoms as measured by the BPRS, PANSS, YMRS, CGI, and CGI Severity of Illness scale. The average weight gain was 4.1 kg. After correction for expected weight gain, the mean weight gain over the 8-week period was 3.4 kg. Prolactin and cholesterol remained unchanged. Trends were found for a decrease in T4 and an increase in thyroid-stimulating hormone. Common adverse effects were somnolence, agitation, drowsiness, and headache. No significant findings were noted on repeat ECGs, EPS measures, or ophthalmic examination. The final average treatment dose was 467 mg/day (range 300-800 mg/day).. Quetiapine is suggested to be effective treatment of youths with psychotic disorders and to have a favorable side-effect profile.

Topics: Adolescent; Age Factors; Akathisia, Drug-Induced; Antipsychotic Agents; Dibenzothiazepines; Dyssomnias; Female; Headache; Humans; Male; Pilot Projects; Psychological Tests; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Time Factors

This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders.. Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations.. No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score.. Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Child; Dibenzothiazepines; Drug Administration Schedule; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Tachycardia; Treatment Outcome

This uncontrolled trial examines the safety and effects of quetiapine, a new atypical antipsychotic, in elderly patients with psychotic disorders.. This is an ongoing, multicenter, open-label, 52-week trial of quetiapine in men and women at least 65 years old with DSM-IV psychotic disorders. Patients received quetiapine, 25 to 800 mg/day. Assessments included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions scale (CGI), the Simpson-Angus Neurologic Rating Scale, and the Abnormal Involuntary Movement Scale (AIMS).. An interim analysis was performed at 12 weeks with results from 151 patients. The median total daily dose was 100 mg/day. The most common adverse events were somnolence (32%), dizziness (14%), postural hypotension (13%), and agitation (11%). Extrapyramidal symptom adverse events occurred in 6% of patients. Mean Simpson-Angus Scale total score showed significant (p<.0001) improvement at endpoint; there were no changes in AIMS scores. BPRS total and CGI-Severity of Illness scores showed significant (p<.0001 and p<.01, respectively) improvement at endpoint. No clinically important effects were reported for hematologic or liver function test variables; small changes in mean free levorotatory thyroxine (T4) levels were not associated with substantial changes in mean thyroid-stimulating hormone concentration. Mean corrected QT interval (QTc) was unchanged, but a slight increase in mean heart rate was noted.. Quetiapine was well tolerated in a nonrandomized study of elderly patients and was associated with improvement in symptoms.

Topics: Aged; Aged, 80 and over; Akathisia, Drug-Induced; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Dizziness; Drug Administration Schedule; Female; Humans; Hypotension, Orthostatic; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Sleep; Treatment Outcome

Psychoses are a common clinical problem in patients with Parkinson's disease. Treatment with typical neuroleptics or withdrawal of antiparkinsonian drugs may improve mental symptoms but will worsen the parkinsonism. Quetiapine (Seroquel), ICI 204,636, is a novel antipsychotic medication with a low potential for producing extrapyramidal side effects. In this open-label clinical study of 2 patients with Parkinson's disease, treatment with Seroquel successfully controlled psychotic symptoms without worsening of motor disability.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

We investigated the striatal dopamine-2 (D2) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients (16 with schizophrenic and two with schizoaffective disorder according to DSM-IV) with single photon emission computed tomography (SPECT) using 123I-iodobenzamide (IBZM) as tracer substance. Four patients were treated with the novel antipsychotic compound quetiapine (300-700 mg/day), six with clozapine (300-600 mg/ day) and eight with haloperidol (10-20 mg/day). They were compared with eight healthy controls. Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol. In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group, there were no extrapyramidal motor side-effects (EPS) in the quetiapine and clozapine treatment groups. Therefore, the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS.

Topics: Adult; Antipsychotic Agents; Benzamides; Clozapine; Dibenzothiazepines; Dopamine Antagonists; Female; Haloperidol; Humans; Male; Middle Aged; Neostriatum; Psychotic Disorders; Pyrrolidines; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Tomography, Emission-Computed, Single-Photon

Quetiapine is widely used to treat psychiatric disorders such as major depression, generalized anxiety disorder, dysthymic disorder, and insomnia other than schizophrenia and bipolar disorder. This study investigated the diagnostic distribution of quetiapine use in patients in a psychiatric hospital, the doses of quetiapine prescribed, and the plasma concentrations (Cps) of quetiapine and active metabolites.. We enrolled 107 patients who had been prescribed quetiapine for at least 4 weeks. Diagnoses, demographics, and concomitant medications were recorded. Blood sampling was performed in the morning, approximately 12 h after the before-bed dose of quetiapine.. Diagnoses comprised schizophrenia (n = 25), bipolar disorder (n = 51), major depression (n = 15), dysthymic disorder (n = 9), and others (n = 7). The daily dose (DD) of quetiapine ranged from 25 to 800 (175.9 ± 184.4) mg, with the mean Cp being 105.6 ± 215.3 ng/ml, with a mean Cps/DD ratio of 0.58 ± 0.55 ng/ml/mg. There was a moderate positive linear correlation between the dose and Cps of quetiapine (r = 0.60), and the interpatient variation in Cps/DD ratio was up to 26-fold.. Quetiapine is used in various doses to treat many psychiatric disorders other than psychosis, and it is usually prescribed as a secondary antipsychotic for symptoms such as insomnia or agitation. A wide interpatient variation of the Cps/DD ratio was noticed. Patients of East Asian descent may exhibit a 50% to 100% increase in the Cps/DD ratio for quetiapine compared with patients of Western descent.

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Psychotic Disorders; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders

Parkinson disease (PD) psychosis (PDP) is a disabling non-motor symptom. Pharmacologic treatment is limited to pimavanserin, quetiapine, and clozapine, which do not worsen parkinsonism. A Food and Drug Administration black box warning exists for antipsychotics, suggesting increased mortality in elderly patients with dementia. However, the reasons for higher mortality are unknown.. Expanding on prior work exploring mortality in treated PDP patients, we conducted a retrospective comparison to understand the links between treatment regimen, clinical characteristics, and negative outcomes.. Electronic medical record data extraction included clinically diagnosed PD patients between 4/29/16-4/29/19 and excluded patients with primary psychiatric diagnoses or atypical parkinsonism. Mortality and clinical characteristics during the study period were compared between untreated patients and those receiving pimavanserin, quetiapine, or both agents (combination). Mortality analyses were adjusted for age, sex, levodopa equivalent daily dose (LEDD), and dementia.. The pimavanserin group (n = 34) had lower mortality than the untreated group (n = 66) (odds ratio = 0.171, 95% confidence interval: 0.025-0.676, p = 0.026). The untreated group had similar mortality compared to the quetiapine (n = 147) and combination (n = 68) groups. All treated groups had a higher LEDD compared to the untreated group, but no other differences in demographics, hospitalizations, medical comorbidities, medications, or laboratory values were found between the untreated and treated groups.. PDP patients receiving pimavanserin had lower mortality than untreated patients. We found no other clear differences in clinical characteristics to explain the mortality risk. Prospective randomized trials are needed to definitively identify the optimal PDP treatment regimen and associated risks.

Topics: Aged; Antipsychotic Agents; Dementia; Humans; Levodopa; Parkinson Disease; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Urea

We report a case of refractory psychosis after carbon monoxide poisoning in a 65-year-old woman who attempted suicide by charcoal burning in 2018. On discharge from hospital, she was bedbound, tube-fed, and had limited verbal output. In early 2019, she was able to resume oral feeding and her physical condition improved. However, she started to have paranoid ideas and auditory hallucinations. She was diagnosed as having organic brain syndrome and was prescribed with quetiapine 300 mg every night. Because of the poor clinical response, quetiapine was switched to olanzapine 20 mg every night and augmented with amisulpride and valproate sodium. However, she remained distressed, psychotic, and suicidal. She was then prescribed with clozapine 300 mg every night. Her symptoms improved despite residual auditory hallucinations remained, but she was less distressed about them.

Topics: Aged; Carbon Monoxide Poisoning; Female; Hallucinations; Humans; Olanzapine; Psychotic Disorders; Quetiapine Fumarate

Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics.. Patients with non-affective psychotic disorder from the GROUP study were divided into three groups: AP medication group (APm) (n = 100), AP in combination with other psychotropics (APc) (n = 73), and medication-free (Meds-free) (n = 100). Weight change was examined at inclusion and after three years using a paired-sample t-test. An Independent-sample t-test was performed to evaluate weight change among patients taking clozapine, olanzapine, and quetiapine and individuals not taking these medications. Linear regression was performed to evaluate the association between covariates and weight.. Patients in the APm group [mean = 1.800 kg, t(99)=2.849, 95% CI(0.546, 3.054), p = 0.005] and the APc group [mean = 1.877 kg, t(72)=2.688, 95% CI(0.485, 3.268), p = 0.009] showed significant weight gain. Patients taking clozapine, olanzapine or quetiapine showed significant weight gain compared to those not taking these medications [mean difference=1.707 kg, t(271)= 2.061, 95% CI(0.077, 3.337), p = 0.040)].. Patients receiving APs and APs with other psychotropics gain weight during long-term treatment. It is possible that weight gain is mainly driven by APs.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Longitudinal Studies; Olanzapine; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Risperidone; Weight Gain

Topics: Clozapine; Humans; Neurodegenerative Diseases; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; United States

Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2 years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit-risk assessment.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Female; Humans; Male; Mental Disorders; Middle Aged; Mirtazapine; Off-Label Use; Olanzapine; Psychiatry; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Retrospective Studies; Risperidone; Valproic Acid

Topics: Antipsychotic Agents; Catatonia; Clozapine; Humans; Psychotic Disorders; Quetiapine Fumarate

The study presents a case of a 64-year-old patient with diagnosed Parkinson's disease and coexisting REM sleep disorders (RBD) confirmed in a polysomnographic examination. In this patient, the use of supplementary therapy - quetiapine (50mg/daily) - due to psychotic disorders, resulted in speech disorders with sensory-motor mixed aphasia type. Aphasia occurred on the fourth day after beginning the treatment with atypical neuroleptic. In MRI examination of the head, no "fresh" cerebral ischemia was found. No focal status epilepticus was reported in the video EEG trial. Results. Complete cure occurred after discontinuation of quetiapine administration. Conclusions. Due to the above, the side-effects of quetiapine treatment were assumed as the cause of focal neurological disorders.

Topics: Antipsychotic Agents; Aphasia; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Nonadherence to antipsychotics may cause relapse and hospitalizations in patients with psychotic disorders. The purpose was to quantify and compare the outpatient's nonadherence rates of atypical antipsychotics by objective detection in blood samples.. Totally, 13,217 outpatients with therapeutic drug monitoring (TDM) data of atypical antipsychotics were included. An event of complete nonadherence was defined as an occurrence of undetectable level of a prescribed antipsychotic in the blood sample submitted for TDM. Patients with such an event(s) were defined as nonadherent of the respective drug treatment (outcome). The rates of nonadherence patients were compared between the drugs by logistic regression.. In the study population, 70.2% of the patients were prescribed doses compliant with a schizophrenia diagnosis. The mean olanzapine equivalent dose in the population was 13.4 mg (95% confidence interval (CI): 13.3, 13.6). The frequency of nonadherence patients, regardless of drug, was 3.7% (CI: 3.4-4.0). The nonadherence patient rate was lowest in clozapine-treated patients (2.2%; CI: 1.5-2.8), followed by aripiprazole (2.3%; 1.7-2.8), risperidone (2.4%; 1.6-3.0), quetiapine (2.8%; 2.3-3.2) and olanzapine (4.9%; 4.1-5.3). Users of olanzapine had significantly higher risk of complete nonadherence (Odds ratio: 1.9; CI: 1.6-2.3, p < 0.001) compared to patients treated with other antipsychotics as a group.. In this study, complete nonadherence of atypical antipsychotics, measured as undetectable blood level, was disclosed for ~5% of outpatients with psychotic disorders. The rate of complete nonadherence was significantly higher during olanzapine treatment compared to other atypical antipsychotics. Further studies should investigate if this reflects drug differences in tolerability or other causal relationships.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Outpatients; Psychotic Disorders; Quetiapine Fumarate; Risperidone

This case highlights recurrent low-grade fevers caused by extended-release Quetiapine (Quetiapine XR), a previously unreported side effect, in a patient with Schizophreniform Disorder. While there have been case reports of Quetiapine causing neuroleptic malignant syndrome, there is paucity of data specifically describing recurrent low-grade fevers, with no other accompanying symptoms, caused by Quetiapine XR.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Female; Fever; Humans; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and an elevated level of serum parathyroid hormone (PTH). PHPT presents with a complex set of renal, skeletal, and neuropsychological symptoms. Parathyroidectomy (PTX) is a radical treatment that is recommended for all physically symptomatic patients with PHPT. However, psychiatric symptoms are not considered as an indication for surgery. There remains an important issue from the view of perioperative management of whether PTX should be performed with the presence of uncontrolled psychiatric symptoms or deferred until severe psychiatric symptoms have been controlled. We report a case of mild hypercalcemia that caused severe psychosis in PHPT, which improved dramatically following PTX and resulted in successful postoperative management.. Our patient was a 68-year-old Japanese woman. She was diagnosed with PHPT, which was triggered by mild hypercalcemia. She was due to receive an operation for osteoporosis and kidney stones. She had severe psychosis, despite medication. Blood examinations revealed mild hypercalcemia (10.4 mg/dL, 8.8-10.1 mg/dL) and elevated serum levels of intact PTH (184.0 pg/mL, 10-65 pg/mL).. She was diagnosed with severe psychosis caused by mild hypercalcemia in PHPT.. Although she was treated with 37.5 mg quetiapine and 2 mg risperidone daily, she was excessively sedated and rejected oral treatment. Therefore, we decided to perform the operation.. Immediately following surgery, serum levels of calcium, and intact PTH were normalized. Her psychotic symptoms ceased completely 5 days after surgery.. We emphasize that PHPT presents with various severe psychiatric symptoms, even in mild hypercalcemia. Psychiatric symptoms may be the only salient symptoms in PHPT, and thus clinicians should suspect PHPT in patients with psychiatric symptoms and mild hypercalcemia. Furthermore, PTX is recommended for PHPT-even in the presence of severe uncontrolled psychiatric symptoms, which carries risks for postoperative management-because psychiatric symptoms are expected to improve and good postoperative management is possible.

Topics: Aged; Antipsychotic Agents; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroid Hormone; Parathyroidectomy; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Treatment Outcome

Topics: Antipsychotic Agents; Diabetes Mellitus; Humans; Psychotic Disorders; Quetiapine Fumarate; Renal Insufficiency, Chronic; Tardive Dyskinesia

Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration.. All patients (. At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia.. Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.

Topics: Adult; Benzodiazepines; Female; Humans; Male; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Substance-Related Disorders; Thiazoles

Topics: Antipsychotic Agents; Follow-Up Studies; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

A 76-year-old man presented with complaints of increased confusion, visual hallucinations and decline in memory. He was admitted to the hospital and started on quetiapine 50 mg daily for symptom management. Shortly after, he was diagnosed with Lewy body dementia and started on rivastigmine, a cholinesterase inhibitor (ChEI), at 1.5 mg two times per day. The patient's symptoms continued to worsen and antipsychotics increased for aggressive behaviour. After he became physically aggressive, an extensive medication management review was conducted, prompting an alternative treatment strategy. The quetiapine dose was reduced from 150 mg daily to 12.5 mg daily, his rivastigmine was increased to 3 mg two times per day and all other antipsychotics were discontinued. The up-titration of his rivastigmine after 10 days of therapy was well tolerated with no adverse effects. He demonstrated a clear clinical response to optimised ChEI therapy and low dose quetiapine, showing improvements in alertness and functioning.

Topics: Aged; Antipsychotic Agents; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Hallucinations; Humans; Lewy Body Disease; Male; Psychotic Disorders; Quetiapine Fumarate; Rivastigmine

Topics: Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Autism Spectrum Disorder; Delusions; Dystonia; Female; Hallucinations; Humans; Hypnotics and Sedatives; Intellectual Disability; Lorazepam; Loxapine; Olanzapine; Paranoid Disorders; Psychotic Disorders; Quetiapine Fumarate; Tourette Syndrome

Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies.. Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available.. Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P = 0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P < 0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR < 1 before day 43, HR > 1 after day 43; P = 0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P = 0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P = 0.001).. Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Cohort Studies; Female; Humans; Lewy Body Disease; Male; Middle Aged; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Urea

Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy.. We performed a retrospective chart review of 131 involuntarily admitted patients with schizophrenia or schizoaffective disorder. Our algorithm aimed to delay olanzapine treatment, standardize medications and suggest initiation of clozapine after failure of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at an optimal dosage was 4 weeks or more. Remission was defined using the symptom-severity component of consensus remission criteria. A logistic regression model was applied to identify significant predictors of remission at discharge.. Overall, 74 patients (56%) were in remission at discharge. Non-remitters were hampered from becoming remitters mainly by the presence of negative symptoms. There were no differences in first-line antipsychotics, dosage of antipsychotics at time of response and adherence rates to algorithm-based pharmacotherapy between remitters and non-remitters. Shorter duration of untreated psychosis, favourable early response and less negative symptoms at baseline were identified as independent predictors of remission at discharge.. The importance of early intervention and specific and adequate treatments of negative symptoms is highlighted.

Topics: Administration, Oral; Adult; Algorithms; Antipsychotic Agents; Clozapine; Commitment of Mentally Ill; Drug Therapy, Combination; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Methotrimeprazine; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

Previous studies suggest immunological alterations in patients with first-episode psychosis (FEP). Some studies show that antipsychotic compounds may cause immunomodulatory effects. To evaluate the immunological changes and the possible immunomodulatory effects in FEP, we recruited patients with FEP (n = 67) and matched controls (n = 38), aged 18-40 years, from the catchment area of the Helsinki University Hospital and the City of Helsinki, Finland. Fasting peripheral blood samples were collected between 8 and 10 a.m. in 10 ml PAXgene tubes. We applied the NanoString nCounter in-solution hybridization technology to determine gene expression levels of 147 candidate genes reflecting activation of the immune system. Cases had higher gene expression levels of BDKRB1 and SPP1/osteopontin compared with controls. Of the individual medications used as monotherapy, risperidone was associated with a statistically significant upregulation of 11 immune system genes, including cytokines and cytokine receptors (SPP1, IL1R1, IL1R2), pattern recognition molecules (TLR1, TLR2 and TLR6, dectin-1/CLEC7A), molecules involved in apoptosis (FAS), and some other molecules with functions in immune activation (BDKRB1, IGF1R, CR1). In conclusion, risperidone possessed strong immunomodulatory properties affecting mainly innate immune response in FEP patients, whereas the observed effects of quetiapine and olanzapine were only marginal. Our results further emphasize the importance of understanding the immunomodulatory mechanisms of antipsychotic treatment, especially in terms of specific compounds, doses and duration of medication in patients with severe mental illness. Future studies should evaluate the response pre- and post-treatment, and the possible role of this inflammatory activation for the progression of psychiatric and metabolic symptoms.

Topics: Adolescent; Adult; Antipsychotic Agents; Cytokines; Female; Gene Expression; Gene Expression Regulation; Humans; Immunity, Innate; Immunologic Factors; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Receptors, Cytokine; Risperidone; Up-Regulation; Young Adult

Primary brain calcification (PBC), a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas, typically presents with various neurological and psychiatric symptoms in the fourth or fifth decade of life or later. We present the case of a patient with psychiatric manifestations much earlier than usual, in the second decade of life.. The case of an adolescent female with acute psychotic symptoms, emotional instability, disorganized and suicidal behavior, stereotypical movements, below average intelligence and a three-year history of headaches is reported. Among others, the presentation included tactile hallucinations with secondary hypochondriacal delusions, which are rarely described in this diagnosis. Massive calcinations in the area of the basal ganglia and thalamus were determined by computerized tomography. Other causes of brain calcification were excluded. No causative mutations were found in selected genes. All the symptoms apart from lower intellectual abilities improved with quetiapine and sertraline. The patient showed no side effects.. This case report highlights the successful use of quetiapine for symptomatic treatment of acute psychosis due to PBC in an adolescent without exacerbating extrapyramidal symptoms.

Topics: Adolescent; Adolescent Behavior; Brain Diseases; Calcinosis; Female; Humans; Psychotic Disorders; Quetiapine Fumarate

Minimizing the duration of untreated psychosis and providing comprehensive early intervention including the use of antipsychotics reflects best practice in the treatment of first-episode psychosis (FEP).

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Cardiovascular Diseases; Child; Clinical Decision-Making; Diabetes Mellitus, Type 2; Humans; Psychotic Disorders; Quetiapine Fumarate

Prolactinomas are tumors of the pituitary gland that usually respond very well to treatment with cabergoline. Resistance to cabergoline is very rare, but when it occurs, it is a difficult problem to resolve if the tumor is inoperable.. A 62-year-old white man was treated for a giant macroprolactinoma detected during investigation of a subacute subdural hematoma of the left frontal lobe. The patient was treated with cabergoline for 17 years with a dose ranging from 1.0 mg to 3.5 mg per week. We were not able to normalize his prolactin level, which initially was 14,992 ng/ml and ultimately 1754 ng/ml. The tumor significantly shrank during the follow-up period but persisted. The patient had cardiac valvulopathies that did not worsen. He had an ischemic stroke and developed a psychotic condition that was successfully treated by lowering the cabergoline and administering quetiapine and mirtazapine together. This regimen led to a small increase in the patient's prolactin that returned to previous levels and remained as such until the last medical evaluation. The tumor continued to shrink and had a cystic degeneration in the last evaluation.. Combined use of cabergoline with quetiapine and mirtazapine to treat a psychotic crisis may have contributed to shrinking the tumor in our patient because these antipsychotics have action mediated by growth factors that interfere with growth of pituitary tumors.

Topics: Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Male; Middle Aged; Mirtazapine; Pituitary Neoplasms; Prolactin; Prolactinoma; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Stroke; Treatment Outcome; Tumor Burden

Sexual side-effects are common among those using antipsychotic medication and may result in poor compliance and reduced quality of life. Retrograde ejaculation (RE) has been described occurring with a number of antipsychotic medications (thioridazine, risperidone, iloperidone and clozapine) but there are no guidelines regarding management of antipsychotic-associated RE. Imipramine has been suggested as a treatment for antipsychotic-associated RE in one small study of patients prescribed thioridazine and a case series of patients prescribed iloperidone. Quetiapine is a commonly used antipsychotic and is thought to be associated with less sexual side-effects relative to other antipsychotic medications. This case report describes a 25-year-old man with first episode psychosis who developed RE during treatment with quetiapine which improved with low-dose imipramine. This is the first description of RE occurring with quetiapine and successful treatment of quetiapine-associated RE with imipramine.

Topics: Adult; Antipsychotic Agents; Ejaculation; Humans; Imipramine; Male; Premature Ejaculation; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

Bipolar patients experience sleep disturbances during and between mood episodes. Yet the impact of sleep on treatment with different medications has not been fully explored. The purpose of this paper is to explore the potential impact of poor sleep at baseline on outcomes in a randomized effectiveness trial of quetiapine and lithium.. The Bipolar CHOICE study was a 6-month, parallel group, multisite randomized controlled trial. Participants with bipolar disorder (N = 482; 59% female and age 18-70 years) received quetiapine or lithium. Patients were allowed to also receive adjunctive personalized treatments, which were guideline-informed, empirically-based medications added to treatment as needed. Medication changes were recorded as necessary clinical adjustments (NCA). Fisher's exact tests, mixed-regression models, and Mann-Whitney U tests were used to assess demographic and clinical characteristics as well as whether sleep disturbance would predict outcomes.. 63% of patients had baseline sleep disturbance. Individuals with sleep disturbance had worse bipolar illness severity, greater severity of depression, mania, anxiety, irritability, and psychosis, were less likely to have sustained response (17% vs. 29%; adjusted RR: 0.55, 95% CI: 0.38-0.78, p = 0.0006) and had more NCAs (median 0.71 vs. 0.59, p = 0.03).. Our findings were limited by how we defined sleep disturbance, and by how severity of sleep disturbance was assessed with one item with a non-sleep specific measure.. Baseline sleep disturbance was associated with more severe bipolar symptoms and worse 6-month outcomes. Further research is warranted on improving sleep in bipolar disorder, especially the role of psychosocial interventions.

Topics: Adolescent; Adult; Affect; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Choice Behavior; Female; Humans; Irritable Mood; Lithium Compounds; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Sleep Wake Disorders; Treatment Outcome

This multicenter, observational drug utilization (DU) study (NCT01594996) investigated the profile of patients and specialist providers who prescribed extended release quetiapine fumarate (quetiapine XR) for treatment of major depressive disorder (MDD) across five European countries (Germany, Italy, Romania, Spain, and Sweden). A DU data abstraction form captured information on the characteristics of physicians, patients, and drugs utilized in the medical management of depressive episodes in MDD, where the therapeutic regimen included quetiapine XR. Data were reported descriptively. This analysis included 811 patients. Psychiatric histories indicated a burden of severe MDD in these patients. Patient demographics were similar across countries; however, those in Sweden had a younger mean age. Physicians' ratings of the therapeutic effect of prior treatment with antidepressants suggested the need for an add-on treatment for most patients. Overall, 15.7% of patients initiated quetiapine XR treatment as monotherapy. Presence of psychotic symptoms during depressive episodes predicted treatment with higher than recommended doses of quetiapine XR (odds ratio=3.11; 95% confidence interval: 1.6-6.0). This analysis demonstrated similarities in DU across the countries analyzed, largely in accordance with the recommended dose of quetiapine XR as an adjunctive therapy to antidepressants in MDD (50-300 mg/day).

Topics: Adult; Antidepressive Agents; Delayed-Action Preparations; Demography; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Utilization Review; Europe; Female; Humans; Male; Medication Therapy Management; Middle Aged; Practice Patterns, Physicians'; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate

Antipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents.. We obtained data on mental disorders from the Norwegian Patient Registry on 0-18 year olds who during 2009-2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database.. A total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009-2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%).. When a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Comorbidity; Depressive Disorder, Major; Female; Humans; Incidence; Infant; Male; Mental Disorders; Norway; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Some atypical antipsychotics are associated with metabolic side effects, which are risk factors for gestational diabetes. The authors examined the risk of developing gestational diabetes associated with the continuation of treatment with aripiprazole, ziprasidone, quetiapine, risperidone, and olanzapine during pregnancy compared with discontinuation of these antipsychotic drugs.. Nondiabetic pregnant women who were linked to a live-born infant and enrolled in Medicaid (2000-2010) and who received one or more prescriptions dispensed for an antipsychotic drug during the 3 months before pregnancy were included in the analyses. Among 1,543,334 pregnancies, some expectant mothers at baseline were receiving treatment with aripiprazole (N=1,924), ziprasidone (N=673), quetiapine (N=4,533), risperidone (N=1,824), or olanzapine (N=1,425). For each antipsychotic drug, women with two or more dispensings ("continuers") were compared with women with no dispensings ("discontinuers") during the first half of pregnancy. A generalized linear model and propensity-score stratification were used to obtain absolute and relative risks of developing gestational diabetes, with adjustment for confounders.. Women who continued antipsychotic treatment during pregnancy generally had higher comorbidity and longer baseline antipsychotic use. The crude risk of developing gestational diabetes among continuers compared with discontinuers, respectively, was 4.8% and 4.5% for aripiprazole, 4.2% and 3.8% for ziprasidone, 7.1% and 4.1% for quetiapine, 6.4% and 4.1% for risperidone, and 12.0% and 4.7% for olanzapine. The adjusted relative risks were 0.82 (95% CI=0.50-1.33) for aripiprazole, 0.76 (95% CI=0.29-2.00) for ziprasidone, 1.28 (95% CI=1.01-1.62) for quetiapine, 1.09 (95% CI=0.70-1.70) for risperidone, and 1.61 (95% CI=1.13-2.29) for olanzapine.. Compared with women who discontinued use of an atypical antipsychotic medication before the start of pregnancy, women who continued treatment with olanzapine or quetiapine had an increased risk of gestational diabetes that may be explained by the metabolic effects associated with these two drugs.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Diabetes, Gestational; Female; Humans; Olanzapine; Piperazines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Thiazoles; Young Adult

Patients with dentatorubral-pallidoluysian atrophy (DRPLA) sometimes elicit psychosis. First-generation antipsychotic drugs have been reported to be effective in treating psychotic symptoms associated with the disease. However, little information is available on the benefits of second-generation antipsychotic drugs (SGAs).. We report on a 47-year-old man with DRPLA whose psychotic symptoms were effectively treated with quetiapine, one of the SGAs. He suffered from delusions, auditory hallucinations, and disorganized speech. Initially, other antipsychotic drugs were tried, but were withdrawn because of adverse effects before switching to quetiapine.. Our observations add to the notion that some of the SGAs are useful for ameliorating psychosis in DRPLA.

Topics: Antipsychotic Agents; Humans; Male; Middle Aged; Myoclonic Epilepsies, Progressive; Psychotic Disorders; Quetiapine Fumarate

Antipsychotics produce electroencephalogram (EEG) modifications and increase the risk of epileptic seizure. These modifications remain sparsely studied specifically for atypical antipsychotics. In this context, our study focuses on EEG modifications associated with atypical strict antipsychotic monotherapies.. Electroencephalogram recordings of 84 psychiatric patients treated with atypical antipsychotics in strict monotherapy (clozapine, n = 22; aripiprazole, n = 22; olanzapine, n = 17; risperidone, n = 9; quetiapine, n = 8; risperidone long-acting injection, n = 4; and paliperidone long-acting injection, n = 2) were analyzed. The modifications were ranked according to both slowing and excitability scores.. Electroencephalogram modifications (in 51 subjects, 60.71%) were graded according to 4 stages combining general slowing and sharp slow waves and/or epileptiform activities. The presence of sharp or epileptiform activities was significantly greater for clozapine (90.9%) compared with other second-generation antipsychotics (aripiprazole, 50%; olanzapine, 58.8%; quetiapine, 37.5%; risperidone, 44.4%). Age, duration of disease progression, and diagnosis were not associated as risk factors. Electroencephalogram modifications were associated with lower doses for treatment with quetiapine but not for specific antipsychotics. Electroencephalogram modifications and severe excitability were associated with higher chlorpromazine equivalent doses.. Atypical antipsychotics (clozapine, aripiprazole, quetiapine, olanzapine, and risperidone) induce EEG modifications, and these are significantly greater for clozapine and appear dependent on chlorpromazine equivalent dose. No encephalopathy was observed in these antipsychotic monotherapies, whatever dose.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cerebral Cortex; Clozapine; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Female; Humans; Male; Middle Aged; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Survival Analysis; Treatment Outcome; Urea

Our objective was to report and describe a case of quetiapine-induced dystonia in an older lady with psychosis. Quetiapine is a second-generation antipsychotic and known to be rare in causing extrapyramidal side effects with rates similar to placebo.. There have been few documented cases of quetiapine-induced dystonia. It is important to be vigilant and consider the development of dystonia in patients who may not fit the typical risk profile.

Topics: Antipsychotic Agents; Female; Humans; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Torticollis

Previous studies approved the important roles of CD68, as scavenger receptors, in Alzheimer's disease (AD). The aim of this study was to evaluate the effect of treatment with anti-psychotic drugs and vitamin B12 on the expression levels of CD68 in monocytes of psychotic AD patients.. Expression of CD68 on the monocytes was evaluated in the following groups: 1. age and sex matched healthy controls (Group 1), 2. non-psychotic AD patients (Group 2), 3. psychotic AD patients (Group 3), 4. psychotic AD patients treated with Risperidone (Group 4), 5. psychotic AD patients treated with Risperidone plus vitamin B12 (Group 5), 6. psychotic AD patients treated with Quetiapine (Group 6), psychotic AD patients treated with Quetiapine plus vitamin B12 (Group 7). The expression of CD68 has been performed using flow cytometry technique.. The results showed that CD68 levels were significantly increased in AD patients in comparison to healthy controls and in psychotic AD patients in comparison to non-psychotic AD patients. Treatment with anti-psychotic drugs decreased the expression of CD68. Expression of CD68 has a positive correlation with pain, dementia and mental disorders symptoms in psychotic AD patients.. CD68 may play key roles in the pathogenesis of AD and its complications may be via induction of inflammation. Therefore, it may be concluded that CD68 may be considered as a risk factor for development of AD and also psychotic symptoms in the patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antipsychotic Agents; Case-Control Studies; Drug Therapy, Combination; Female; Flow Cytometry; Humans; Inflammation; Male; Monocytes; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Vitamin B 12

Topics: Adult; Antipsychotic Agents; Diagnosis, Differential; Female; Hallucinations; Humans; Porphyria, Acute Intermittent; Psychotic Disorders; Quetiapine Fumarate; Twins, Monozygotic

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Double-Blind Method; Humans; Psychotic Disorders; Quetiapine Fumarate

Objective Despite many women suffering from psychosis in their childbearing years, limited data exist about the use of atypical antipsychotic agents in pregnancy. Atypical antipsychotic agents are often used to treat bipolar disorder, instead of lithium or valproate because of the known teratogenicity of those agents. As well, atypical antipsychotics are often prescribed in anxiety disorders and depression. This study sought to describe pregnancy outcomes for women prescribed atypical antipsychotics during pregnancy. Methods This retrospective review included all cases treated by Auckland Maternal Mental Health services in which atypical antipsychotic agents were utilized during pregnancy over three years. Results Over the three years, 45 pregnant women were prescribed atypical antipsychotic agents, most commonly quetiapine or olanzapine. Two-fifths (40%) were diagnosed with bipolar disorder and almost one-third (31%) with a psychotic disorder. Two-thirds (64%) were prescribed multiple psychotropic medications during their pregnancy. Instrumental delivery rates were elevated at 38%. A minority (13%) of the women developed gestational diabetes mellitus. Although 7% of infants were born premature, all were born after 35 weeks. Two major malformations were noted, similar to baseline community rates. Conclusions This naturalistic study adds to the limited literature about treatment with atypical antipsychotic agents in pregnancy, though not adequately powered to detect small differences in malformations or obstetrical outcomes. It also highlights the myriad of indications for which pregnant women are prescribed atypical antipsychotics, and the multiple other risk factors seen in this population.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Maternal Health Services; Mental Health Services; Olanzapine; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Young Adult

Psychotic disorders in Parkinson's disease (PDPD) are common and significantly influence the quality of life and disability level. The pathogenesis of PDPD is complex and not yet fully understood. Taking into consideration the features of the Parkinson's disease (usually older patients with a risk of cognitive decline), and the pharmacodynamics of the antiparkinsonian and traditional antipsychotic drugs, the management of PDPD is a challenging issue of clinical neurology and psychiatry. In this systematic review, scientific publications for the period 2014-2016 were analyzed within two bibliographic databases: MEDLINE/PubMed and eLIBRARY.RU. Additionally, the guidelines of the International Parkinson and Movement Disorders Society, American Academy of Neurology and European Academy of Neurology were included in the analysis. Clozapine is recommended to use in the treatment of PDPD, quetiapine is possible to use, pimavanserin will probably become a remedy of choice. Nonpharmacological approaches have positive effects on the general condition of the patients with PDPD, however the efficacy of such approaches to treat psychosis is unclear.. Психотические расстройства при болезни Паркинсона (ПРБП) отмечаются у большого числа пациентов. Они оказывают значительное влияние на качество жизни и уровень инвалидизации. Патогенез ПРБП является сложным и до конца не изученным. Принимая во внимание специфику БП (как правило, пациенты пожилого возраста с риском появления когнитивных нарушений), а также фармакодинамические особенности антипаркинсонических и классических антипсихотических средств, лечение ПРБП требует особого внимания неврологов и психиатров. Представлен систематический обзор, в котором обобщены результаты научных публикаций за период 2014-2016 гг. в двух библиографических базах данных: MEDLINE/PubMed и eLIBRARY.RU, а также клинических рекомендаций Международного общества болезни Паркинсона и нарушений движения, Американской и Европейской академий неврологии. Из антипсихотических средств клозапин является препаратом, рекомендованным к применению, кветиапин - препарат, который признается возможным к применению, пимавансерин, вероятно, станет одним из препаратов выбора в терапии ПРБП. Нефармакологические методы лечения оказывают положительный эффект в плане улучшения общего состояния пациентов с ПРБП, однако их эффективность по лечению собственно ПРБП остается неясной.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Urea

In psychiatric clinical practice, there is a need to identify psychotropic drugs whose metabolisms are prone to be altered with increased inflammatory activity in an individual patient.. The aim of this study was to find out whether elevated serum levels (≥5 mg/l) of C-reactive protein (CRP), an established laboratory marker of infection and inflammation, are associated with increased serum concentrations of the atypical antipsychotic drugs clozapine, quetiapine, and risperidone.. Therapeutic drug monitoring request forms of patients whose antipsychotic drug concentrations had been measured under conditions of normal (<5 mg/l) and pathological (>5 mg/l) levels of C-reactive protein were retrospectively screened. The serum concentrations in relation to the daily doses [concentration per dose (C/D) (ng/mL/mg)] and the metabolic ratios [ratio of concentrations (metabolite/drug)] were compared intraindividually by the Wilcoxon signed rank test. To the study effects of the intensity of infections on drug concentrations, C-reactive protein and C/D levels were submitted to Spearman's correlation analysis.. Elevated levels of C-reactive protein were found in 105 patients. They were significantly associated with elevated values in C/D for clozapine (n = 33, P < 0.01) and risperidone (n = 40, P < 0.01). A trend for an increase was found for quetiapine (n = 32, P = 0.05). Median increases were 48.0 % (clozapine), 11.9 % (quetiapine), and 24.2 % (active moiety of risperidone), respectively.. In patients who exhibit signs of inflammation or infection with increased C-reactive protein values during psychopharmacological treatment, especially under clozapine and risperidone, therapeutic drug monitoring is recommendable in order to minimize the risk of intoxications due to elevated drug concentrations.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Biomarkers; C-Reactive Protein; Clozapine; Female; Humans; Inflammation; Male; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Risperidone; ROC Curve

Topics: Adult; Antipsychotic Agents; Encephalitis; Female; Glucocorticoids; Hashimoto Disease; Humans; Prednisolone; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR).. Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8 weeks (schizophrenia = 153, major depression = 200, bipolar depression = 252, other psychiatric conditions = 60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS).. The mean dose of quetiapine XR during follow-up was 195.6 ± 154.8 mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7 ± 0.1 points and 25.1 ± 0.9 points. Adverse events were observed in 34 and 26 % of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS ≥20 points (n = 292, 43 %) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C ≥5, n = 610, 93 %) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence.. Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR. Clinicaltrials.gov registration number NCT02409823.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Patient Compliance; Prospective Studies; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Schizophrenia; Sleep Stages; Treatment Outcome; Weight Gain

With the development of various imaging techniques, the deformation-based morphometry (DBM) method provides an objective automatic examination of the whole brain.. This study aims to assess the abnormalities in the brains of first-episode schizophrenia (FES) patients treated with quetiapine using another advanced nonrigid registration method, hierarchical attribute matching mechanism for elastic registration, through the application of DBM in the entire brain.. Thirty FES patients and 30 normal controls were grouped by age and handedness and subjected to magnetic resonance imaging examination. The patients had relatively short durations of untreated psychosis (DUP; 6.4 ± 5.2 months), and only a single antipsychotic drug, quetiapine (dosage, 200 ± 75 mg), was used for treatment. Statistically significant changes in regional volume were analyzed via DBM. In addition, a voxel-wise analysis of correlations between the duration of treatment or dosage and volume was also performed.. Compared with control subjects, FES patients showed contracted regions located in Brodmann area (BA) 42 and BA 19. By contrast, expanded regions were observed in BA 38, BA 21, BA 6 and 8, and left cerebellum. A negative correlation was observed between dosage and volume in the hippocampus, while a positive correlation was found in the caudate. Meanwhile, a negative correlation was observed between duration of treatment and volume in BA 38.. Both regional volume reductions and increases were detected in the brains of FES patients treated with quetiapine compared with healthy control subjects. Such differences may be partially relevant to dosage and treatment duration in clinic.

Topics: Adult; Antipsychotic Agents; Brain; Case-Control Studies; Cerebral Cortex; Dibenzothiazepines; Female; Functional Laterality; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Occipital Lobe; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

In 2004, the American Diabetes Association (ADA) released treatment guidelines recommending metabolic screening for children and adolescents before and after initiation of second-generation antipsychotics. Prior studies showed that the guidelines coincided with a small increase in glucose testing of children and adults but had limited follow-up. This study sought to evaluate changes in metabolic screening of children initiating second-generation antipsychotics around the time of the 2004 guidelines and in the following eight years.. Study patients (N=52,407) were identified in a large nationwide commercial insurance claims database for the period January 1, 2003, through December 31, 2011. The study population was a cohort of nondiabetic new users of second-generation antipsychotics who were ages 5-18. Glucose and HbA1c tests completed before and after second-generation antipsychotic initiation were identified with Current Procedural Terminology-4 codes. Metabolic screening was also examined by second-generation antipsychotic agent prescribed and psychiatric diagnosis.. The proportion of patients receiving a glucose test preinitiation increased from 17.9% in 2003 to 18.9% in 2004, and testing postinitiation increased from 14.7% to 16.6% in the same period. The slight increase in glucose testing was not sustained; the proportion tested dropped in the following years before rising again in 2008. Glucose screening was most common for patients taking aripiprazole. Patients with a diagnosis of hyperkinetic disorder were less likely to be tested. HbA1c testing was less frequent but had a similar usage pattern.. The small improvement in metabolic screening immediately after the 2004 ADA guidelines were issued was not sustained. Overall, metabolic screening rates remained suboptimal throughout the study period.

Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Blood Glucose; Child; Child, Preschool; Cohort Studies; Conduct Disorder; Databases, Factual; Depressive Disorder; Diabetes Mellitus; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hyperkinesis; Male; Mass Screening; Mental Disorders; Olanzapine; Piperazines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Thiazoles

Topics: Adult; Drug Overdose; Female; Humans; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Restless Legs Syndrome

To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics.. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMI<30 kg/m²) and obesity grade 2-3 in 38 patients (BMI>30 kg/m²).. Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these. we developed recommendations for management of patients treated with second generation antipsychotics.. Цель исследования - установление частоты и особенностей пищевого поведения у больных шизофренией при лечении антипсихотиками второго поколения. Материал и методы. Выборку составили 56 пациентов, 48 женщин и 8 мужчин, с диагнозами 'шизофрения' и 'шизоаффективное расстройство'. Их средний возраст был 28±4,5 года. Больные лечились рисперидоном, кветиапином и оланзапином. Исследование включало клинико-анамнестический, эндокринологический методы и тестирование стереотипа пищевого поведения с помощью специального опросника DEBQ. У всех обследованных были выявлены избыточная масса тела или ожирение: избыточная масса тела 1-й степени - у 18 пациентов (ИМТ до 30 кг/м2) и ожирение 2-3-й степени - у 38 (ИМТ более 30 кг/м2). Результаты и заключение. Выявлены разные типы нарушений пищевого поведения - экстернальный, ограничительный и эмоциогенный и зависимость их частоты и выраженности от пола, лечебного препарата, наличия и степени ожирения. На основе полученных данных были сформулированы рекомендации в отношении тактики ведения пациентов, находящихся на терапии антипсихотиками второго поколения.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Feeding and Eating Disorders; Female; Humans; Male; Obesity; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine.. This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis.. After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively.. Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

Topics: Adolescent; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Blood Pressure; Body Mass Index; British Columbia; Child; Child Development Disorders, Pervasive; Child, Preschool; Cholesterol; Cholesterol, HDL; Cohort Studies; Dyslipidemias; Female; Humans; Incidence; Longitudinal Studies; Male; Mental Disorders; Metabolic Syndrome; Mood Disorders; Obesity; Overweight; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Waist Circumference

We present the case of a 19-year-old who developed psychotic symptoms after exposure to a potentially rabid animal and post-exposure prophylactic treatment. This case serves to remind physicians to fully explore the possibility of a nonpsychiatric origin of de novo psychotic symptoms and provides indirect evidence in favor of the possible involvement of the immune system in the development of psychotic disorders.

Topics: Adult; Anti-Anxiety Agents; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Clonazepam; Diagnosis, Differential; Dibenzothiazepines; Female; Haloperidol; Humans; Lorazepam; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Rabies; Rabies Vaccines; Young Adult

A 27-year-old man treated with quetiapine for anxiety disorder developed hypertriglyceridaemia-induced acute pancreatitis and diabetic ketoacidosis. He was otherwise physically healthy with no family history of hyperlipidaemia. Despite aggressive intensive therapy he died of multiorgan failure within 36 h from initial presentation. While second-generation antipsychotics are well known to be causally linked to diabetes and hyperlipidaemia, this is to my knowledge the first-described case of a fatal triad of extreme hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine. Clinicians should be aware of this rare clinical presentation since rapid progression to multiorgan failure can occur. Early supportive therapy should be initiated. Lactescent serum and ketoacidosis in severe acute pancreatitis should not be overlooked-initiate insulin therapy and possibly plasmapheresis in case of extreme hypertriglyceridaemia.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed Diagnosis; Diabetic Ketoacidosis; Diagnosis, Differential; Dibenzothiazepines; Dose-Response Relationship, Drug; Fatal Outcome; Humans; Hypertriglyceridemia; Male; Pancreas; Pancreatitis, Acute Necrotizing; Phobic Disorders; Psychotic Disorders; Quetiapine Fumarate; Tomography, X-Ray Computed

Priapism is rarely related to use of non-erectile related medications. The objective was to educate about the multiple possible causes of priapism and to provide treatment recommendations for the different types of priapism. We present the case of a 43-year-old African American male with a history of schizoaffective disorder who presented to our emergency department multiple times over a three year period with priapism, each episode related to the ingestion of quetiapine. Following penile aspiration and intercavernosal injection of phenylephrine, this patient had resolution of his priapism. This case demonstrates an unusual case of recurrent priapism.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Emergency Service, Hospital; Humans; Male; Priapism; Psychotic Disorders; Quetiapine Fumarate; Recurrence

We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.

Topics: Adult; Aggression; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Pregnancy; Psychotic Disorders; Puerperal Disorders; Quetiapine Fumarate

For patients with comorbid complex posttraumatic stress disorder (PTSD) and psychotic disorder, trauma-focused therapy may be difficult to endure. Phase-based treatment including (a) stabilization, (b) trauma-focused therapy, and (c) integration of personality with recovery of connection appears to be the treatment of choice.. The objective of this article is to describe and evaluate the therapeutic process of a single case from a holistic perspective.. We present a case report of a 47-year-old woman treated for severe complex PTSD resulting from repeated sexual and physical abuse in early childhood and moderate psychotic symptoms stemming from Dandy Walker Syndrome with hydrocephalus.. The patient was treated with quetiapine (600-1,000 mg) and citalopram (40 mg). Stabilization consisted of intensive psychiatric nursing care in the home and stabilizing group treatment for complex PTSD. After stabilization, the following symptom domains showed improvement: self-regulation, self-esteem, assertiveness, avoidance of social activities, and negative cognitions. However, intrusions and arousal persisted and were therefore subsequently treated with prolonged imaginary exposure that also included narrative writing assignments and a final closing ritual. This intensive multidisciplinary, phase-based approach proved effective: All symptoms of complex PTSD were in full remission. Social integration and recovery were promoted with the reduction of polypharmacy and the provision of social skills training and lifestyle training.. The present case shows a phase-based treatment approach with multidisciplinary collaborative care to be effective for the treatment of a case of complex PTSD with comorbid psychotic disorder stemming from severe neurological impairment. Replication of this promising approach is therefore called for.

Topics: Adult Survivors of Child Abuse; Antipsychotic Agents; Citalopram; Comorbidity; Dandy-Walker Syndrome; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Middle Aged; Psychotherapy, Group; Psychotic Disorders; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; China; Cohort Studies; Dibenzothiazepines; Double-Blind Method; Earthquakes; Humans; Irritable Mood; Longitudinal Studies; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk Factors; Sleep Wake Disorders; Suicide; Suicide Prevention; Suicide, Attempted; Survivors; Treatment Outcome

Topics: Acute Generalized Exanthematous Pustulosis; Antipsychotic Agents; Dibenzothiazepines; Drug Eruptions; Female; Humans; Intellectual Disability; Middle Aged; Psychotic Disorders; Quetiapine Fumarate

The association between the use of antipsychotics and diabetes mellitus (DM) is still unclear, as depicted by several conflicting reports. Our study aims to assess the risk of DM in new users of antipsychotics.. Our nested case-control study used the Quebec Health Insurance Board databases. People in the source cohort were DM-free and had initiated an antipsychotic treatment. Subjects were cohort members who initiated an antidiabetic or had a diagnosis of DM during their follow-up period. Three variables were used to assess antipsychotic exposure: the antipsychotic used (any typical, clozapine, olanzapine, quetiapine, risperidone, or more than 1 drug); the number of 30-day periods of use; and antipsychotic use at index date (current or past). A paired multivariate logistic regression model was used to calculate adjusted odds ratios.. Among the 88 467 people included in the cohort, 6109 subjects with DM were identified and were matched to 61 090 control subjects. New users of quetiapine were less likely to develop DM than new users of typical antipsychotics (OR, 0.89; 95% CI 0.81 to 0.99). The risk of DM was not statistically different across the atypical antipsychotics. A longer exposure to any antipsychotic (for each 30-day period, OR 1.009; 95% CI 1.006 to 1.011) and current use of antipsychotics (OR 1.26; 95% CI 1.17 to 1.36) were associated with DM.. These results suggest that metabolic parameters of people exposed to antipsychotics should be monitored, irrespective of the drug taken, among the drugs available at the time of analysis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Clozapine; Cohort Studies; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Time Factors; Young Adult

Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine) have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines), particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results.. A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS) in new users of risperidone compared to new users of FGAs.. After controlling for potential confounders (demographics, comorbidity and medication use), risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22-0.67; 0.45, 95% CI: 0.28-0.73; 0.50, 95% CI: 0.33-0.77; 0.65, 95% CI: 0.45-0.94, respectively). At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54-1.05.. In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Canada; Dementia; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Phenothiazines; Proportional Hazards Models; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone

Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition associated with the use of antipsychotics and other drugs that influence dopaminergic transmission. Although NMS is typically associated with classical antipsychotics, it can also be induced by atypical antipsychotics. In this paper, we report a case of NMS associated with clozapine use.. A 27-year-old male was diagnosed as schizophrenia in 2006 and zuclopenthixol depot was administered parenterally. Following the second injection, NMS was diagnosed and he was switched to clozapine. After 4 years of clozapine use, one day, he suddenly stopped eating, stayed in bed all day, and had incontinence. Upon examination at our hospital the patient had muscle rigidity, high fever, leukocytosis, and a high creatine phosphokinase level, and NMS was diagnosed. He was put on bromocriptine. NMS resolved, but psychotic relapse and catatonia developed. 10 sessions of electro convulsive treatment (ECT) were administered. Quetiapine 25 mg/day was introduced and titrated up to 600 mg/day afterwards. He has been using quetiapine 600 mg/day for 18 months and at the time this manuscript was written has not had any signs of psychosis or NMS.. NMS is usually induced by the use of agents with high dopaminergic affinity. Incomplete or extraordinary NMS cases have been reported due to clozapine and atypical antipsychotics. The presented case is noteworthy due to the complete and typical presentation of NMS. It should always be kept in mind that all atypical antipsychotics including clozapine have the probability to induce NMS although not common.

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Creatine Kinase; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Serotonin Antagonists

No safe, tolerated, and effective treatment for Parkinson's disease psychosis (PDP) is available; however, clozapine and quetiapine are often used off-label. An ideal PDP drug should have a therapeutic window that alleviates psychotic symptoms at doses that allow for maintained motor control and do not cause sedation. The present study determined the effective doses of quetiapine, clozapine, and the nondopaminergic, selective 5-HT2A inverse agonist/antagonist, pimavanserin, in an animal model of PDP and compared them with the doses that caused dopamine blockade and sedation. Augmented amphetamine-induced locomotion in rats with bilateral substantia nigra lesions was used to assess antipsychotic efficacy, whereas blockade of apomorphine-induced rotations in rats with unilateral 6-hydroxydopamine lesions was used to assess antidopaminergic action and reduction in spontaneous locomotion was used to assess sedation. The estimated therapeutic ratios for clozapine and quetiapine varied between 0.81 and 3.3. In contrast, the estimated therapeutic ratios for pimavanserin were at or above 170. These results suggest that a selective 5-HT2A inverse agonist/antagonist, such as pimavanserin, may provide distinct advantages compared with clozapine or quetiapine as a therapy for PDP.

Topics: Amphetamine; Animals; Antiparkinson Agents; Antipsychotic Agents; Apomorphine; Clozapine; Dopamine; Dose-Response Relationship, Drug; Male; Parkinsonian Disorders; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Urea

Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001-2005) was analyzed focusing on outpatients, aged 6-17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (χ(2) = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (χ(2) = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57-1.61) for olanzapine, 1.03 (95% CI: 0.59-1.81) for quetiapine, 0.85 (95% CI: 0.43-1.70) for aripiprazole, and 1.22 (95% CI: 0.60-2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Dibenzothiazepines; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Medication Adherence; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

To investigate the influence of a single episode of psychiatric inpatient treatment on metabolic parameters.. A total of 294 consecutive patients of an Upper Austrian psychiatric department were assessed at admission and discharge regarding bodyweight, body mass index (BMI), high density cholesterol (HDL), low density cholesterol (LDL), triglycerides (TG) and fasting glucose (FG), and the TG/HDL ratio.. Patients showed an increase of BMI of 0.35 kg/m² (+ 1.3%) during a mean duration of inpatient stay of 25.8 days. LDL rose by 10.7 mg/dl (+ 8.1%), triglycerides by 23.0 mg/dl (+ 17%), HDL decreased by 4.4 mg/dl (-7.4%). Fasting glucose decreased by 3.6 mg/dl (-3.8%), yet the TG/HDL ratio, as a marker for insulin resistance, increased significantly from 2.86 to 3.58 (+ 25.2%) on average. Patients with psychotic disorders gained about three times more weight than patients with other diagnoses. Negative alterations of serum lipids were to be found in all diagnostic groups but were especially pronounced in patients with psychotic disorders who were treated with second-generation antipsychotics clozapine, olanzapine and quetiapine.. Psychiatric inpatient treatment leads to clinically relevant deterioration of metabolic parameters within a short time, most pronouncedly in patients with psychotic disorders.

Topics: Antipsychotic Agents; Austria; Benzodiazepines; Biomarkers; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Clozapine; Dibenzothiazepines; Female; Glucose; Hospitalization; Humans; Insulin Resistance; Length of Stay; Lipid Metabolism; Male; Mental Disorders; Middle Aged; Multivariate Analysis; Olanzapine; Polypharmacy; Prospective Studies; Psychiatric Department, Hospital; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Triglycerides; Weight Gain

: The use of antipsychotic medications is associated with an increased risk of death in older adults with dementia. The risk of death in patients with preexisting parkinsonism who receive antipsychotic drugs is not known.. : Using a nested case-control design, we examined the risk of death within 30 days of newly starting antipsychotic medications among people with Parkinsonism aged 70 years and older in Ontario, Canada. Data were obtained from Ontario's healthcare administrative databases.. : Among 5,391 individuals with parkinsonism who died during the study period (2002-2008) and a matched comparison group of 25,937 who were still alive, individuals exposed to atypical antipsychotic drugs had a higher risk of death (unadjusted odds ratio [OR] = 2.8, 95% CI: 2.1-3.8, adjusted OR: 2.0, 95% CI: 1.4-2.7). Results were similar for quetiapine use compared with no antipsychotic use (unadjusted OR: 2.5, 95% CI: 1.6-4.0, adjusted OR = 1.8, 95% CI: 1.1-3.0). Typical antipsychotics were associated with an increased odds of death compared with atypical antipsychotics (unadjusted OR = 2.4, 95% CI 1.1-5.2, adjusted OR = 2.4, 95% CI: 1.1-5.7).. : Individuals with parkinsonism who are newly prescribed antipsychotic medications have a higher risk of death within 30 days than those who do not start these medications. Although it is not possible to establish causality, the results suggest an increased risk. It is important to be vigilant for accompanying serious medical conditions that may increase mortality in individuals requiring treatment with antipsychotics and to consider alternative approaches to treating psychosis, agitation, and aggression in this population.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cohort Studies; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Ontario; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk; Risperidone

Quetiapine apparently differs from other antipsychotic drugs in terms of its antidepressant activity and efficacy in bipolar depression. The mechanism of this activity is unknown although it may be mediated by its metabolite N-desalkylquetiapine (norquetiapine).. The aim of the study was to analyse the relationships between quetiapine and norquetiapine plasma concentrations and clinical improvement in depressive and anxious symptoms.. This was a prospective observational study. Recruited patients were evaluated during a clinical post-acute phase. Patients were recruited from patients hospitalized in the Psychiatric Department of Ospedale Maggiore Policlinico of Milan, Italy. After discharge they were followed-up as outpatients. The study involved 41 outpatients (23 males, 18 females; age >18 years) diagnosed as affected by schizophrenia (17 patients), borderline personality disorder (eight patients) or bipolar depression (16 patients) on the basis of the Diagnostic and Statistical Manual of Mental Disorders, fourth text revision (DSM-IV-TR) criteria. Patients were prescribed 50-800 mg of quetiapine (Seroquel®). Patients were evaluated after discharge from the psychiatric department (baseline, T0), after 15 days (T1) and after 3 months (T2) using the Brief Psychiatry Rating Scale (BPRS) with particular reference to the dimensions of depression (items 5, 9 and 13) and anxiety (items 1, 2 and 6). Plasma quetiapine and norquetiapine concentrations were determined by means of high-performance liquid chromatography at T2.. There was a significant improvement in the mean BPRS total score, as well as in the dimensions of anxiety and depression. The bipolar patients only showed a significant curvilinear relationship described by a second-order polynomial model between the plasma norquetiapine/quetiapine concentration ratio and the improvement in depression at T2. There was a significant negative linear correlation between the norquetiapine/quetiapine ratio and anxiety in all of the patients.. The results of this study confirm the efficacy of quetiapine on both anxious and depressive symptoms. Norquetiapine has a specific effect on anxiety and depressive symptoms, showing a correlation between plasma concentrations and clinical efficacy only in patients with bipolar depression.

Topics: Adult; Antipsychotic Agents; Anxiety; Depression; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate

Objective of this observational trial is to examine the effects of quetiapine in comparison with olanzapine and risperidone on clinical outcomes and quality of life in patients with schizophrenia and schizoaffective disorder in routine care. 374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine, or risperidone at discharge from inpatient treatment were included. Clinical and psychosocial outcomes were assessed before discharge and at 6, 12, 18, and 24 months. Statistical analyses were conducted by mixed-effects regression models for longitudinal data. The propensity score method was used to control for selection bias. Patients discharged on olanzapine had significantly lower hospital readmissions than those receiving quetiapine or risperidone. The average chlorpromazine equivalent dose of quetiapine was higher than in patients treated with olanzapine or risperidone. No further significant differences between treatment groups were found. Quetiapine and risperidone are less effective in preventing the need for psychiatric inpatient care than olanzapine, and higher chlorpromazine equivalent doses of quetiapine are needed to obtain clinical effects similar to those of olanzapine and risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Hospital Administration; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Selection Bias; Survival Analysis; Time Factors; Treatment Outcome

A patient's death due to severe hematologic adverse effects of the concomitant use of four psychotropic medications is reported.. A 40-year-old Caucasian woman with a 9-year history of depression and anxiety (managed with alprazolam) was admitted to a psychiatric hospital for the treatment of acute psychotic symptoms. After nine days, the patient was discharged home on a regimen of lamotrigine, mirtazapine, quetiapine, and venlafaxine. Five weeks later, the development of severe ocular cellulitis, severe oral thrush, and febrile neutropenia necessitated the woman's urgent rehospitalization; on admission, her white blood cell count was 600 cells/mm(3), her absolute neutrophil count was 18 cells/mm(3), and microbial pathogens were isolated in peripheral blood and tracheal aspirate cultures. Despite treatment with antibiotics and filgrastim, the patient developed multiorgan dysfunction and died five days later from septic shock. The woman's concomitant use of multiple psychotropics and the late recognition of drug-induced agranulocytosis likely contributed to her severe symptoms and ultimate death. The application of the Naranjo scale to this case yielded a score of 6, indicating a probable adverse drug reaction. Although hematologic adverse effects have been reported with the use of each of the four drugs implicated in the woman's death, this is thought to be the first report of fatal agranulocytosis associated with any of the drugs.. A 40-year old woman with a history of acute psychotic symptoms developed agranulocytosis and neutropenia after starting therapy that included lamotrigine, mirtazapine, quetiapine, and venlafaxine.

Topics: Adult; Agranulocytosis; Antidepressive Agents, Second-Generation; Antimanic Agents; Antipsychotic Agents; Blood Cell Count; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Fatal Outcome; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lamotrigine; Mianserin; Mirtazapine; Multiple Organ Failure; Neutropenia; Orbital Cellulitis; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Recombinant Proteins; Shock, Septic; Triazines; Venlafaxine Hydrochloride

This study was conducted to explore the efficacy and tolerability of quetiapine extended release (XR) to treat psychosis and accompanying acute behavioral disturbance in hospitalized psychiatric patients.. Patients with psychosis who displayed aggression were administered quetiapine XR (day 1 mean dose: 293.3 mg). Symptoms and side effects were assessed prospectively over an 8-day period. Symptoms were measured by the Overt Aggression Scale and Brief Psychiatric Rating Scale (BPRS), and side effects were measured using the Simpson-Angus Scale and Barnes Akathisia Rating Scale.. Fifteen of 16 consenting patients completed the study. Aggression was significantly reduced by day 3. Psychopathology also was significantly reduced, with the greatest improvement in BPRS Thinking Disturbance subscale scores. No significant increase in movement side effects was seen by day 8. Seven participants were administered a concomitant sedating antipsychotic on an as-needed basis, particularly in the first 4 days of treatment; these participants displayed much greater aggression--but not psychopathology--at day 1, and it took longer for their aggression and psychopathology to improve compared with patients treated with quetiapine XR as the sole antipsychotic.. Further research is needed before definitive recommendations can be made. However, current findings provide tentative support for quetiapine XR as a safe and effective medication for treating concurrent psychosis and behavioral disturbance, particularly in less severely aggressive patients.

Topics: Acute Disease; Adult; Aggression; Antipsychotic Agents; Brief Psychiatric Rating Scale; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Inpatients; Male; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Brain Injuries; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

In the healthy population, several pathways are known to exert an effect on basal metabolic factors. Previous studies have found associations between single nucleotide polymorphisms in clock genes or downstream hormone receptors such as the leptin receptor (LEPR) or glucocorticoid receptor (NR3C1) and obesity in the healthy population, but this association remains to be examined in patients with schizophrenia treated with antipsychotics.. To assess anthropomorphic parameters in patients taking second-generation antipsychotics (SGA) as a function of nine polymorphisms in three core genes of the clock pathway, and two genes of downstream hormone receptors.. Clinical parameters were evaluated in 261 patients with schizophrenia spectrum disorder. Polymorphisms in LEPR, MC3R, NR3C1, PER2 and SDC3 were genotyped. In order to control for multiple testing, permutation tests were used to generate corrected empirical p-values using the Max(T) procedure in PLINK.. A significant effect of the rs6196 polymorphism in the NR3C1 on weight (β=-4.18; SE=2.02; p=0.018), BMI (β=-1.88; SE=0.64; p=0.004), waist (β=-5.77; SE=1.75; p=0.001) and waist/hip ratio (β=-0.03; SE=0.012; p=0.009) was found. Permutation tests confirmed the findings for BMI (p=0.037) and waist (p=0.024). Carriers of the G allele consistently displayed better parameters than patients with the wild type allele. A weak effect of rs4949184 in SDC3 on BMI was found, but this did not sustain permutation testing (β=-1.27; SE=0.58; p=0.030, p=0.270 after permutations).. Variations in genes implicated in circadian regulation or its related downstream pathways may be important in the regulation of antropomorphic parameters in patients with schizophrenia during long-term treatment with SGA.

Topics: Adult; Age Factors; Alleles; Amisulpride; Anthropometry; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Composition; Body Mass Index; CLOCK Proteins; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Female; Genetic Association Studies; Genetic Carrier Screening; Genotype; Humans; Long-Term Care; Male; Middle Aged; Mutation, Missense; Olanzapine; Period Circadian Proteins; Piperazines; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptor, Melanocortin, Type 3; Receptors, Glucocorticoid; Receptors, Leptin; Risperidone; Schizophrenia; Sex Factors; Sulpiride; Syndecan-3

Rapid weight gain among patients with mental disorders can further compound psychological distress and negatively influence compliance. Weight gain associated with treatment with atypical antipsychotic medication has been widely recognized as a risk factor for the development of diabetes type II and cardiovascular diseases. This paper describes a 33-year old female patient treated for schizoaffective disorder. Within two months after introducing quetiapine the patient experienced considerable weight gain amounting to 19 kg. The replacement of antipsychotic during inpatient psychiatric care resulted in weight loss.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Dibenzothiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Metabolic Syndrome; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Thiazoles; Weight Gain

A delusion of parasitosis can be idiopathic or due to different somatic or psychiatric disorders. We report on a 48-year-old man who suffered from imagined animals in his nose. A somatic cause could not be found so that we diagnosed an idiopathic delusion of parasitosis. Later, Wegener's granulomatosis, a rare form of autoimmune induced vasculitis, was diagnosed. It was treated successfully with immunosuppressiva. The psychotic symptoms which remitted under risperidone did not return after finishing the neuroleptic medication.

Topics: Antipsychotic Agents; Delusions; Dibenzothiazepines; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Male; Middle Aged; Nasal Cavity; Parasitic Diseases; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Substitution; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia

The present study aims to evaluate effectiveness of antipsychotics in a cohort of chronic outpatients affected by schizophrenia and related disorders.. Three hundred chronic patients affected by schizophrenia (n=173), schizoaffective (n=117) and delusional (n=60) disorder who were in treament with antipsychotics on 1.3.2008 were considered in the study; effectiveness of antipsychotic treatment was evaluated by means of rates of all cause discontinuation in a 12 months period (31.3.2008-31.3.2009) and of "overall duration of treatment" (DT) (duration of treatment retrospectively evaluated on the basis of clinical records+duration of treatment prospectively evaluated during the 12-months follow up).. Discontinuation of treatment was registered in 25% of patients (29% due to side effects, 14% due to scarce adherence, 11% due to lack of efficacy, 22% due to more causes). Clozapine (7%), Risperidon Long-acting (10%), Typical Antipsychotics depot (11%) and Olanzapine were associated to lower rates of all causes discontinuation. Overall mean duration of antipsychotic treatment was 18± 32 months, with statistically significant differences between drugs (F=4.65, p=0.000). Clozapine (65 mo), Olanzapine (50 mo), butyrophenones (49 mo), typical antipsychotics depot (48 mo), and risperidone (47.5 mo) were the antipsychotics with a longer duration of treatment. Only Clozapine showed a significantly longer DT than any other antipsychotic medication excluding buthyrrohenones.. Rates of all cause discontinuation of antipsychotics appear to be somewhat lower than expected on the basis of pragmatic studied published in the last years; similarly overall duration of treatment seems to be longer. Clozapine is associated to a higher overall effectiveness respect to any other atypical antipsychotic.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Butyrophenones; Clozapine; Delayed-Action Preparations; Delusions; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Patient Dropouts; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Young Adult

To identify the factors associated with newly prescribed, first-line, second-generation antipsychotics (SgAs) associated with weight gain-olanzapine, risperidone, and quetiapine.. Retrospective medical record review.. Outpatient and inpatient psychiatry services at a tertiary care, academic medical center.. Three hundred forty consecutive adults who had major depressive disorder with psychotic features, bipolar I, bipolar II, bipolar not otherwise specified, or schizoaffective disorder over two time periods (August 30-October 30, 2009, and April 1-May 31, 2010).. Clinical and sociodemographic variables associated with newly prescribed olanzapine, risperidone, and quetiapine were identified by using univariate and multivariate logistic regression. Several clinical factors were individually associated with initiation of these SgAs: mania (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.2-10.8, p=0.02), psychosis (OR 3.3, 95% CI 1.5-6.9, p=0.002), and inpatient treatment (OR 3.8, 95% CI 1.8-7.9, p=0.0005). Prevalent use of lithium (OR 0.3, 95% CI 0.1-0.9, p=0.03) and being married (OR 0.3, 95% CI 0.1-0.8, p=0.02) were inversely associated with new use of an SgA. Mania, psychosis, married status, and lithium use remained independently associated on multivariate analysis. Factors related to metabolic or vascular risk were not associated with SgA initiation.. Psychiatric clinicians were influenced heavily by clinical features related to mental status and acuity when determining whether to prescribe SgAs. However, factors related to vascular risk were not associated. Future observational studies should consider current clinical status as an important factor in determining propensity to receive antipsychotics or other short-term treatments for bipolar and related disorders.

Topics: Academic Medical Centers; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

The aim of our study was to assess the time to 'first improvement' associated with specific atypical (AAP) and typical (TAP) antipsychotic drugs in patients with early-onset schizophrenia and other related psychotic disorders.. This study involved a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs and TAPs, for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 296 teenage patients (141 males, 155 females; mean age 16.0 ± 1.5 years). The time to first improvement could be estimated in 258 patients; of these, 195 patients (76%) had been treated with AAPs and 63 patients (24%) with TAPs. We found that most patients were taking risperidone (N = 96), followed by olanzapine (64 patients). Other patient numbers were as follows: ziprasidone (16 patients), quetiapine (12 patients), clozapine (7 patients), haloperidol (15 patients), perphenazine (28 patients), and sulpiride (20 patients).. The mean time to first improvement was 6.9 (± 4.2) days in the AAP group and 5.8 (± 3.5) days in the TAP group; the difference was significant at the trend level (p=0.063). With respect to individual drugs, the mean time to first improvement was 7.1 (± 4.1) days for risperidone, 6.7 (± 4.2) days for olanzapine, 6.5 (± 5.2) days for ziprasidone, 6.1 (± 4.4) days for quetiapine, 7.4 (± 3.0) days for clozapine, 5.2 (± 2.4) days for haloperidol, 5.9 (± 3.8) days for perphenazine, and 6.0 (± 3.9) days for sulpiride. Differences among drugs were not significant (p=0.680).. Analysis revealed a significant group level trend indicating that typical antipsychotic drugs have faster onsets of action than atypical antipsychotic drugs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Medical Records; Olanzapine; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride; Thiazoles; Time Factors; Treatment Outcome

Malignant neuroleptic syndrome (MNS) is a serious and potentially fatal side-effect of neuroleptic treatment. Beside antipsychotic drugs, other psychotropic drugs such as antidepressants and lithium carbonate can cause this life threatening side-effect. Underlying mechanism of this side-effect is still unknown and debated. So far some risk factors have been identified, with clinical observations and recent pharmacogenetic research suggesting (with inconsistent findings) correlation between genetic mechanisms and predisposition to MNS. Polymorphisms of CYP2D6 enzyme through which most psychotropic drugs are metabolized and TaqIA DRD2 which is target for antipsychotic drugs could be the link between pharmacogenetic factors and potential for development of MNS. In this paper we present two case reports with clinical presentation of three consecutive MNS. One patient developed MNS while he was taking combination of drugs: first time haloperidol, promazine and fluphenazine, second time fluphenazine and perazine and third time clozapine, promazine and valproic acid consecutively. The other patient developed MNS while taking following combination of drugs: first time haloperidol and lithium carbonate, second time risperidone and third time clozapine consecutively. Pharmacogenetic analysis for CYP2D6 and TaqI A DRD2 polymorphisms for both patients was done. Genotypisation of CYP2D6*1*3*4*5*6 in both patients showed no evidence of poor metabolizer phenotype. On the other hand, first patient was heterozygous for CYP2D6*4 (genotype *1/*4). CYP2D6 polymorphisms could have clinical significance because may lead to toxicity and unwanted side-effects in standard usual antipsychotic dose ranges. Analysis Taql A DRD2 polymorphism for first patient showed that he is heterozygous for A1 allele (genotype A1A2) which is commonly associated with predisposition to MNS. According to our literature three consecutive MNS are rarely described, and incidence of MNS generally is too low to perform clinical research. Many patophysiological mechanisms may probably underlie this complex and potentially fatal syndrome, still unknown etiology. But, genetic mechanisms could be significant. Further pharmacogenetic research, findings and analysis in patients who develop single or repeated MNS are strongly recommended. In long term, pharmacogenetic analysis, implemented in daily clinical practice, could help in prevention of this extremely serious side-effect.

Topics: Adult; Alleles; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cytochrome P-450 CYP2D6; Dibenzothiazepines; Drug Therapy, Combination; Fluphenazine; Genetic Carrier Screening; Genotype; Haloperidol; Humans; Lithium Carbonate; Male; Neuroleptic Malignant Syndrome; Perazine; Polymorphism, Genetic; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Recurrence; Risperidone

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders.. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups.. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p < 0.001 for all comparisons), total cholesterol increased in the bipolar (p = 0.02) and psychotic (p = 0.01) disorder groups, low-density lipoprotein cholesterol increased in the bipolar group (p = 0.02), and free T4 decreased in the psychotic disorder group (p = 0.05). More patients with bipolar disorder presented overweight plus > or = 1 obesity-related complication at follow-up.. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Biomarkers; Bipolar Disorder; Body Mass Index; Child; Cholesterol, LDL; Chromatography, High Pressure Liquid; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Obesity; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thyroxine; Treatment Outcome; Weight Gain

The aim of this paper is to highlight the association between antipsychotic medication, in this instance paliperidone, and hyperprolactinaemia, and discuss the impact of this adverse effect on patient management.. Four patients with paliperidone-induced hyperprolactinaemia are described with a brief review of the literature.. Four female patients aged between 20 and 50 years developed hyperprolactinaemia 3 weeks to 4 months after commencement of treatment with paliperidone. The levels were significantly raised above the normal upper limit of 500 mIU/L, ranging between 1500 and 3996 mIU/L, and returned to within the normal range after cessation of the medication (82-381 mIU/L). Two of the patients were asymptomatic despite significant elevation of prolactin; two experienced galactorrhoea, a distressing adverse effect. Subsequent management was significantly affected.. Routine standardized monitoring of prolactin levels may guide treatment choice, avoiding potential disruption to the therapeutic relationship, enhancing compliance with future medication and preventing negative treatment outcomes. Detailed education should accompany the monitoring process and include discussion of the risks of associated adverse effects of antipsychotic medications versus the benefit of significant symptom relief.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Galactorrhea; Humans; Hyperprolactinemia; Isoxazoles; Middle Aged; Paliperidone Palmitate; Patient Compliance; Piperazines; Prolactin; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Quinolones; Recurrence; Schizophrenia, Paranoid; Young Adult

Availability of new psychotropic agents, and formulations, as well as expanded indications for previously available agents, has had an impact on prescribing patterns in community psychiatric practice. This study tracked changes in patient diagnostic profiles and compared antipsychotic prescribing patterns for patients managed by a continuing care team over a 2.25-year period.. Data pertaining to patient diagnoses and psychotropic medications was obtained from sequential cross-sectional file review and the pharmacy database. Data were collected in late 2004 (n = 224) and early 2007 (n = 294).. The majority of patients suffered from DSM-IV schizophrenia, schizoaffective and related disorders (68% in 2004, 71% in 2007). Second generation antipsychotic (SGA) medications (79% in 2004, 99% in 2007 of all antipsychotics) were the most widely used agents. Use of quetiapine as a proportion of all oral SGAs increased (8% to 17%) as did that of long-acting risperidone (<1% to 17% of all antipsychotics) paralleled by a decline in long-acting first generation antipsychotic agents (15% to <1%). Significant changes in the prescription of non-benzodiazepine hypnotics and mood stabilizers were also noted.. Statistically significant changes in prescribing patterns of antipsychotics during the study period were noted. Likely causes are discussed.

Topics: Administration, Oral; Anticonvulsants; Antipsychotic Agents; Case Management; Community Mental Health Centers; Cross-Sectional Studies; Delayed-Action Preparations; Dibenzothiazepines; Drug Utilization; Humans; Hypnotics and Sedatives; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Urban Population; Victoria

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptors, Dopamine D2; Severity of Illness Index

Topics: Adult; Antipsychotic Agents; Cross Reactions; Dibenzothiazepines; False Positive Reactions; Female; Humans; Male; Methadone; Middle Aged; Mood Disorders; Psychotic Disorders; Quetiapine Fumarate; Substance Abuse Detection

Comparative effectiveness analyses using retrospective databases may be highly sensitive to common design decisions employed by researchers.. To test the sensitivity of statistical results to common research methods in retrospective database analyses. Comparisons of time to all-cause discontinuation (TTAD) across antipsychotic drug therapies are used to illustrate these effects.. Data from the California Medicaid Program were used to identify 231,635 episodes of antipsychotic drug therapy. Four sequential analyses of TTAD were performed on all patients, patients with 1 year of post-treatment data, and patients with schizophrenia and using models that included variables documenting drug treatment history.. Patients using atypical antipsychotics consistently achieve longer TTAD than patients treated with conventional antipsychotics. Nevertheless, estimated differences narrowed when analyses included only patients with schizophrenia. Risperidone performed better than olanzapine when diagnosis was not limited to schizophrenia, and quetiapine outperformed olanzapine and risperidone when the analysis did not control for treatment history. This latter result reflects the disproportionate use of quetiapine in long-duration augmentation episodes. There were no statistical differences across alternative atypical antipsychotics once the analysis excluded patients without a diagnosis of schizophrenia and included patient treatment history in the analysis.. Comparative effectiveness analyses of alternative drug therapies are sensitive to diagnosis and patient drug treatment history. Data on these factors can be derived from paid claims data and should be used to provide more accurate comparisons of effectiveness across drugs and to provide results that cover the full range of clinical scenarios that clinicians face.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; California; Databases, Factual; Decision Making; Dibenzothiazepines; Female; Humans; Male; Medicaid; Middle Aged; Olanzapine; Patient Selection; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone; Schizophrenia; United States; Young Adult

The aim of the current study was to evaluate quetiapine doses used across diagnosis categories in a sample of psychiatric inpatients.. Discharge letters of all adult inpatients who had received quetiapine between 1999 and 2005 were retrospectively reviewed. Logistic regressions were carried-out to assess links between quetiapine discharge dosage (> or =800 mg/day vs. <800 mg/day), diagnostic categories, substance abuse or dependence, benzodiazepine discharge doses, age and sex.. The data of 231 patients were included. Five hundred and for discharge documents were analyzed: 113 for psychotic disorders, 190 for personality disorders, 134 for bipolar and schizoaffective bipolar disorders, 29 for unipolar depression or anxiety disorders, and 35 for mental retardation. Considering psychotic disorders as a reference group, patients with personality disorders were statistically significantly less likely to be in the high quetiapine dosage group at discharge (P = 0.007, OR = 0.1 and CI [0.03; 0.6]).. Quetiapine seems to be used in a variety of clinical situations, with a wide range of doses and a lower dosage in patients treated for personality disorders.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Cross-Sectional Studies; Depressive Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Patient Discharge; Patient Readmission; Personality Disorders; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies

Naturalistic studies offer advantages over randomized clinical trials by including patients seen in routine practice. Aripiprazole and quetiapine are the most recent second-generation antipsychotics available in the United Kingdom. We aimed to study all patients who were prescribed these medications in a defined geographic area in order to identify and compare those who had a good clinical response.. We conducted an electronic chart review of a sample of all people attending secondary mental health care in the county of Lanarkshire, Scotland, who were treated with aripiprazole or quetiapine for schizophrenia and related psychoses (ICD-10 criteria) between 2002 and 2007. To measure effectiveness, we retrospectively assigned Clinical Global Impressions (CGI) scores and examined medication discontinuation rates.. Eighty-nine patients were started on treatment with aripiprazole and 132 patients with quetiapine over the 5-year period. Those treated with quetiapine had a higher initial illness severity (CGI-Severity of Illness scale) (p = .0003), were more likely to be starting rather than switching antipsychotics (p = .0003), were more likely to have a mood disorder (p = .03), were less likely to be treatment resistant (p = .005), and had lower rates of prescription of additional antipsychotics (p = .009). After adjusting for these variables, the proportions who improved according to CGI were 74% with aripiprazole and 67% with quetiapine. Overall medication discontinuation rates were also similar, 42% for aripiprazole and 45% for quetiapine, with early discontinuation of aripiprazole being noticeable, often due to agitation (13% of all patients treated with the drug).. Despite their different pharmacologic properties, aripiprazole and quetiapine were similarly effective in the majority of patients. Early discontinuation of aripiprazole due to agitation was an important finding.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Medical Records Systems, Computerized; Mental Health Services; Patient Dropouts; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Schizophrenia; Severity of Illness Index

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Therapy, Combination; Haloperidol; Humans; Intellectual Disability; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Young Adult

The objective of this study was to examine the predictors associated with adherence to atypical antipsychotic medication following discharge from hospital for children and adolescents with first-episode psychosis. Sixty-five children and adolescents, age 15.35 +/- 2.08 years, 59% boys, who had participated in a longitudinal cohort study examining relapse following first hospitalization for episode of psychosis were included in this study. All those studied were discharged on one of three atypical antipsychotics, risperidone, quetiapine, or olanzapine between January 1999 and October 2003. Time 1 data were collected retrospectively from medical charts using a standardized questionnaire; time 2 data were obtained using questionnaire mailed to participants' parents a minimum of 2 years post-discharge, mean 3.9 +/- 1.3 years. Variables examined as predictors of adherence fell into broad categories of biological, social and treatment variables. Discharge on concurrent pharmacologic agent for affective symptoms in addition to atypical antipsychotic, OR = 10.5 [95% confidence interval (CI) = 2.06-53.19] was a strong predictor of medication adherence in adolescents. The results indicated that children and adolescents discharged from their first hospitalization following a psychotic episode may be more likely to stay on prescribed antipsychotic medication if they are prescribed concurrent medication for affective symptoms.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Cohort Studies; Dibenzothiazepines; Epidemiologic Studies; Female; Humans; Length of Stay; Male; Olanzapine; Patient Compliance; Patient Discharge; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Treatment Outcome; United States

Two weeks after starting the oral contraceptive pill, a 16-year-old girl developed increasingly violent chorea and an evolving psychosis with prominent hallucinations, ideas of reference, and paranoia. An erythematous skin rash subsequently developed and Sydenham's chorea (SC) was diagnosed. Following neuroleptic medication and steroids, her chorea and psychosis subsided. This case illustrates that severe psychotic features can occur in SC. It is recommended that antistreptolysin O titres and antibasal ganglia antibodies are checked early in patients with evolving movement disorders and prominent neuropsychiatric features, as the window for modifying the course of this immune-mediated disorder may be narrow.

Topics: Adolescent; Antipsychotic Agents; Antistreptolysin; Basal Ganglia; Chorea; Contraceptives, Oral; Dibenzothiazepines; Female; Hallucinations; Humans; Methylprednisolone; Neuroprotective Agents; Paranoid Disorders; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Steroids; Streptococcal Infections

The objective of this study was to illustrate the implications of using standardised psychotic relapse definitions by comparing published clinical trial relapse and drop-out rates for patients with schizophrenia.. Relapse definitions from three published placebo-controlled clinical trials were standardised to facilitate pair-wise retrospective comparison of relapse outcomes in patients with schizophrenia receiving extended-release quetiapine fumarate (quetiapine XR), paliperidone extended release (paliperidone ER) and olanzapine. Relapse definitions were based on changes in the Positive and Negative Syndrome Scale score, Clinical Global Impression-Severity score and predefined Brief Psychiatric Rating Scale positive items. Economic implications of relapse outcomes were also calculated. A limitation of this study is that this was not a head-to-head comparison. In addition, patient-level data were lacking for the paliperidone ER and olanzapine studies.. When the relapse definition from the paliperidone study was applied to the quetiapine XR clinical trial data, 14 quetiapine XR patients (15%) relapsed compared with 23 (22%) in the paliperidone ER study. According to the olanzapine relapse definition, three quetiapine XR patients (3.2%) experienced a relapse compared with nine patients (4.0%) in the olanzapine study. An illustrative calculation of potential economic impact associated with these standardised relapse rates implied incremental expenditures ranging from 74.8 million pound sterling to 373.9 million pound sterling (2006 pound sterling) for paliperidone ER versus quetiapine XR treatment and no material difference with olanzapine.. The results show that the definition of relapse has a significant impact on relapse outcomes, and associated economic implications, and that relative drug efficacy can only be considered when results are based on standardised relapse criteria.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Isoxazoles; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Placebos; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Recurrence; Retrospective Studies; Treatment Outcome; Young Adult

The purpose of this article is to review the utilization and dosing of ziprasidone in a state hospital system and to compare the dosing to dosing recommendations contained in product labeling that suggest a starting dose of 40 mg/day and a target dose range of 40 to 160 mg/day for schizophrenia.. Dosing of ziprasidone was examined from the time when it was first marketed in 2001 up to and including calendar year 2006 using a database that contains patient information and drug prescription information for every inpatient within the adult civil facilities of the New York State psychiatric hospital system operated by the New York State Office of Mental Health. Supporting evidence for a therapeutic dose response for ziprasidone was examined by conducting a PubMed search for the period January 1, 1990, to June 1, 2008, identifying English-language articles related to ziprasidone dose in schizophrenia using the search terms ziprasidone, dose, and schizophrenia.. Although the highest efficacious dose of ziprasidone recommended in the manufacturer's product label is 160 mg/day, the mean dose of ziprasidone prescribed among patients hospitalized in New York State in calendar year 2006 and receiving antipsychotic medication (N = 7154) was 179 mg/day (N = 709), with 51.6% receiving doses in excess of 160 mg/day (N = 366). Patients discharged on treatment with ziprasidone (N = 189) received a mean dose of 206 mg/day. Patients with schizophrenia with a history of prior state hospital admission were more likely to receive doses greater than 160 mg/day. Clinicians in hospitals with the highest prescribing rates for ziprasidone were more likely to prescribe ziprasidone in excess of 160 mg/day. The initial dose on the first day for new starts on treatment with ziprasidone was 91 mg/day (N = 112). Published anecdotal reports describe the use of ziprasidone in excess of 160 mg/day and up to 640 mg/day among patients not responding to lower doses, but, currently, there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy.. Dosing of ziprasidone in a large state hospital system is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of ziprasidone in excess of 160 mg/day, controlled clinical trials are needed to determine if these higher doses are more effective.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Utilization; Female; Hospitalization; Hospitals, Psychiatric; Hospitals, State; Humans; Male; Piperazines; Prescription Drugs; Product Labeling; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome

Quetiapine is an atypical antipsychotic that is believed to have a low D2 binding affinity in striatal and extrastriatal regions. We report the case of a female patient with the diagnosis of schizoaffective disorder (using DSM-IV-TR criteria) who initially received amisulpride for 3 months, discontinued gradually because of persistent and distressing extra-pyramidal symptoms, and who developed tardive dyskinesia 3 months later after the initiation of quetiapine. A trial with ziprasidone resulted in a further worsening of tardive dyskinesia symptoms. A further trial with aripiprazole, improved her tardive dyskinesia symptoms. Although, it is under consideration the possibility that the improvement could have been due to the discontinuation of quetiapine, we conclude that aripiprazole improved the TD symptoms.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Sulpiride; Thiazoles

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Dibenzothiazepines; Epilepsy; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Middle Aged; Psychotic Disorders; Quetiapine Fumarate

The goal of this study was to examine provider prescribing habits following carbamazepine discontinuation and to assess for the presence of antipsychotic-related adverse drug reactions due to the loss of car-bamazepine-related induction of the cytochrome P450 enzyme (CYP) 3A4 and p-glycoprotein.. A retrospective chart review of patient records from January 2006 through December 2007 at the Veterans Affairs (VA) San Diego Healthcare System was done, which focused on the co-prescription of carbamazepine and a second-generation (atypical) antipsychotic (aripiprazole, quetiapine, risperidone) that is significantly affected by CYP3A4/p-glycoprotein induction. The cases in which carbamazepine was discontinued while the antipsychotic was continued during the 2-year time frame were then analyzed further. Data were collected concerning documentation of antipsychotic-related adverse drug reactions that occurred after carbamazepine was discontinued and prescribers' responses to carbamazepine discontinuation.. Nine patients were identified who had concomitant prescriptions for carbamazepine and a second-generation antipsychotic and who then discontinued carbamazepine. In only one case did the provider initially decrease the dose of the antipsychotic when carbamazepine was discontinued. Two patients experienced akathisia 3 weeks after carbamazepine was discontinued.. Many providers are not adjusting the dose of second-generation antipsychotics after discontinuation of a CYP3A4/p-glycoprotein inducer, placing patients at risk for adverse drug reactions. In addition to provider education, mechanisms need to be integrated into the current prescription processing software to alert providers of kinetic changes related to medication discontinuation. In addition, when discontinuing carbamazepine in patients who are being concomitantly treated with a second-generation antipsychotic that is a CYP3A4/p-glycoprotein substrate, providers should arrange for patient follow-up 2-4 weeks after carbamazepine discontinuation to evaluate patients for antipsychotic-related adverse drug reactions.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Carbamazepine; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Enzyme Induction; Female; Humans; Male; Medical Audit; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risk Factors; Risperidone

Antipsychotics have been used in the therapy of schizophrenia and bipolar disorder and several second generation antipsychotics (SGA) are already available in Hungary. The clinical trials' results are confusing in regarding the differences in the efficacy of the SGA's, but the differences in their side-effects are clear. Considering its most important side-effects, such as extrapyramidal symptoms, weight gain, metabolic syndrome and prolactin level elevation, quetiapine has a fairly good side effect profile, and can therefore be recommended especially in case of bipolar patients who are highly sensitive towards side effects.. In our case-report, we present four patients who were successfully treated with quetiapine for their psychotic mood elevation.

Topics: Adult; Affect; Antipsychotic Agents; Dibenzothiazepines; Drug Therapy, Combination; Euphoria; Female; Humans; Isoxazoles; Male; Medication Adherence; Middle Aged; Paliperidone Palmitate; Prolactin; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain

In comparison to metabolic syndrome, edema seems to be a rare occurrence in antipsychotic treatment.. In this paper, we report on two subjects with psychotic disorders who were found to have peripheral edema during olanzapine therapy.. The theoretical background and the relevance of this observation are examined. Furthermore, edema as a side effect of antipsychotic treatment is reviewed. In particular, the importance of olanzapine, a commonly used neuroleptic drug, as a possible causative substance is evaluated.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Therapy, Combination; Edema; Female; Humans; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Psychotic Disorders; Quetiapine Fumarate; Substance Withdrawal Syndrome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; DiGeorge Syndrome; Female; Humans; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Anti-Bacterial Agents; Antipsychotic Agents; Clarithromycin; Dibenzothiazepines; Drug Interactions; Drug Overdose; Humans; Male; Metabolic Syndrome; Psychotic Disorders; Quetiapine Fumarate

The goal of this study was to select some genes that may serve as good candidates for future studies of the direct effects (not explained by obesity) of some antipsychotics on hyperlipidemia. A search for single-nucleotide polymorphisms (SNPs) that may be associated with these direct effects was conducted. From a published cross-sectional sample, 357 patients on antipsychotics were genotyped using a DNA microarray with 384 SNPs. A total of 165 patients were taking olanzapine, quetiapine or chlorpromazine which may directly cause hypertriglyceridemia or hypercholesterolemia. Another 192 patients taking other antipsychotics were controls. A two-stage statistical analysis that included loglinear and logistic models was developed to select SNPs blindly. In a third stage, physiological knowledge was used to select promising SNPs. Known physiological mechanisms were supported for 3 associations found in patients taking olanzapine, quetiapine or chlorpromazine [acetyl-coenzyme A carboxylase alpha SNP (rs4072032) in the hypertriglyceridemia model, and for the neuropeptide Y (rs1468271) and ACCbeta, (rs2241220) in the hypercholesterolemia model]. These genes may be promising candidates for studies of the direct effects of some antipsychotics on hyperlipidemia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cross-Sectional Studies; Dibenzothiazepines; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Lipids; Male; Olanzapine; Oligonucleotide Array Sequence Analysis; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Leucopenia and neutropenia could be side effects of anti-psychotic drugs, especially clozapine. However, there is evidence that other anti-psychotics can cause leucopenia and neutropenia. We present the clinical follow-up and treatment process of a patient, who had initially developed quetiapine and amisulpride related neutropenia, but not with aripiprazole.

Topics: Adult; Amisulpride; Antipsychotic Agents; Aripiprazole; Blood Cell Count; Dibenzothiazepines; Female; Humans; Leukopenia; Neutropenia; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Sulpiride

This study examined the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly in the United States.. The study involved analysis of household and prescription files of the Medical Expenditure Panel Survey (MEPS) data from 1996 to 2004. The analysis focused on the use of six atypical antipsychotic agents namely, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole among the elderly of 60 years or older. Multiple logistic regression analysis within the conceptual framework of Andersen's Behavioral Model was used to examine the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly.. An average of 0.62 million elderly received antipsychotic agents annually during the study period. A majority of the elderly using antipsychotic agents were female (70%), white (86%), non-Hispanic (95%), and living in metropolitan statistical areas (79%). Frequently reported diagnoses among the elderly taking antipsychotic agents were dementia (26.12%), anxiety (20.42%), and schizophrenia (6.62%). Of the elderly receiving antipsychotic agents, 50.39% received atypical agents and 51.88% received typical agents during the study period. The most frequently used atypical agents were risperidone, olanzapine, and quetiapine. Multivariate logistic regression analysis revealed that need (perceived mental health, p < 0.01) and enabling (time, p < 0.01) factors were significantly associated with atypical antipsychotic use after controlling for predisposing factors. The study found that elderly patients with relatively poor perception of mental health (need) and utilization of antipsychotic agents after 1998 (enabling) were more likely to involve the use of atypical agents.. This study was limited to the use of antipsychotic agents in community settings and cannot be extrapolated to other settings. Correlates examined in this study were limited to variables available from the data source and those used by previous researchers.. Need and enabling factors play a vital role in the use of atypical agents in the elderly. The findings have important implications in understanding the use and outcomes of atypical agents in the elderly. Future pharmacoepidemiological research can use these variables to control for confounding and selection bias when evaluating health care outcomes in observational studies.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Anxiety; Benzodiazepines; Cross-Sectional Studies; Dementia; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Residence Characteristics; Risperidone; Schizophrenia; Serotonin Antagonists; United States

The aim of this study was to investigate the steady-state pharmacokinetic, safety, and tolerability profiles of immediate-release quetiapine administered by similar dose-escalation regimens in pediatric and adult populations with psychotic or mood disorders.. Pediatric patients aged 10-17 years were titrated to a quetiapine dose of 200 mg twice daily (b.i.d. on days 5-7, 400 mg b.i.d. on days 11-12, with a final 400-mg dose on day 13. In a separate trial, adult patients aged 18-45 years were titrated to a quetiapine dose of 200 mg b.i.d. on days 4-6, 400 mg b.i.d. on days 10-11, with a final 400-mg dose on day 12. Concentrations of quetiapine and three metabolites (quetiapine sulfoxide, 7-hydroxy quetiapine, and norquetiapine) were quantified in plasma and urine. Adverse events, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests were evaluated throughout the studies.. In both pediatric and adult populations, plasma concentrations of quetiapine and norquetiapine increased proportionately as the dose was escalated from 200 mg b.i.d. to 400 mg b.i.d. There were no age-related differences in the dose-normalized quetiapine plasma concentration-time curve (AUC(SS)) and maximum plasma concentration (C(SS,max)). Quetiapine was rapidly absorbed after 200-mg and 400-mg doses in pediatric patients [median t(max) (time to maximum plasma concentration) 1.5 hours, both doses] and adult patients (median t(max) 1.0 hour and 1.2 hours, respectively). The mean quetiapine t(1/2) (terminal elimination half-life) was approximately 6 hours for pediatric and 5 hours for adult patients. Norquetiapine displayed a similar median t(max) and a longer t(1/2) compared with quetiapine. Quetiapine was well tolerated, with no serious adverse events and no unexpected events reported.. Pediatric and adult populations demonstrated similar pharmacokinetic, safety, and tolerability profiles for quetiapine administered by dose escalation. The predictability in quetiapine concentration profiles for children aged 10 years to adults suggests that no dosage adjustment may be required when treating patients of these ages.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Area Under Curve; Child; Dibenzothiazepines; Electrocardiography; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate

To investigate 3-month changes in glucose metabolism in a naturalistic sample of patients with schizophrenia newly started on or switched to specific atypical antipsychotic medication therapy.. One hundred eighty-three patients were evaluated before initiation and 3 months after with a 75-g glucose load oral glucose tolerance test (OGTT). Data were collected between November 2003 and January 2007.. Eight patients (4.4%) developed new-onset diabetes within 3 months. Initiation of clozapine resulted in a significantly higher risk for new-onset glucose abnormalities than initiation of aripiprazole (odds ratio = 67.29, 95% CI = 5.23 to 866.49). Significant drug x time interactions were found for all OGTT glucose assessments (fasting: F = 6.79, df = 5,177; p < .0001; 30 minutes: F = 3.89, df = 5,177; p = .0023; 60 minutes: F = 5.03, df = 5,177; p = .0002; 120 minutes: F = 3.78, df = 5,177; p = .0028), with the evolution of plasma glucose levels being significantly worse in patients initiated on clozapine therapy (fasting, 30 minutes, and 60 minutes), olanzapine therapy (fasting, 60 minutes, and 120 minutes), and quetiapine therapy (fasting and 60 minutes) than in patients initiated on aripiprazole therapy (p < .05). Clozapine was also significantly more deleterious than risperidone and amisulpride for fasting plasma glucose level changes (p < .05). Type of initiation (start or switch) did not affect any of the metabolic parameters.. The incidence of new-onset glucose abnormalities, including diabetes, in the first 3 months after newly starting or switching atypical antipsychotic medication is high and may be markedly influenced by type of prescribed antipsychotic. The importance of accurately screening for new-onset glucose abnormalities after initiation of an atypical antipsychotic is emphasized.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Fasting; Feeding Behavior; Female; Glucose; Glucose Tolerance Test; Humans; Incidence; Insulin; Male; Middle Aged; Olanzapine; Piperazines; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Time Factors

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Health Care Costs; Humans; Informed Consent; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy; Haloperidol; Humans; Olanzapine; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Topics: Aged; Alzheimer Disease; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Delirium; Depressive Disorder; Diagnosis, Differential; Dibenzothiazepines; Hallucinations; Humans; Male; Olanzapine; Oxazepam; Psychotic Disorders; Quetiapine Fumarate; Tachycardia

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Thiazoles

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Psychotic Disorders; Quetiapine Fumarate; Risk Factors

Clinical efficacy, safety and tolerability of quetiapine in the treatment of 23 hospitalized psychotic adolescents were evaluated retrospectively. Twelve patients were changed to quetiapine from another antipsychotic medication during their hospital stay. In these patients, CGI-S improved from 4.75+/-0.87 to 2.92+/-0.67 (observation period 3.7+/-1.6 months). The most common adverse events were transient tachycardia and sedation. Mild EPS occurred only in one patient under quetiapine monotherapy. Transaminase increases more than threefold above norm were observed in two patients. fT4 values were slightly below the norm in 67% of the cases. In 11 patients, quetiapine was initiated using a rapid titration schedule with high dosages in the acute phase. Receiving a mean maximum daily dose of 927+/-300 mg, CGI-S improved from 6.00+/-0.63 to 3.18+/-1.25 (observation period 2.9+/-1.8 months). Severe adverse events did not occur. Besides applying lorazepam temporarily in nine of the 11 patients, antipsychotic co-medication was not necessary in this group. In line with other studies, quetiapine may be considered as an effective treatment for adolescents with a severe psychotic disorder showing a favourable side-effect profile. Our preliminary data suggest that a rapid initiation with high doses could be a promising approach in acute psychotic adolescents.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Hospitalization; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia

We report a case of a 29-year-old man with schizoaffective disorder in which diabetes mellitus and hypertriglyceridemia developed with quetiapine (Seroquels). We reviewed the literature on the relationship between antipsychotic therapy and development of metabolic disorders and found serious concerns. This case demonstrates the importance of a careful monitoring of glucose and other metabolic parameters in patients receiving atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Diabetes Mellitus; Dibenzothiazepines; Humans; Hypertriglyceridemia; Male; Psychotic Disorders; Quetiapine Fumarate; Risk Factors

Late-onset bipolar disorder is rare and can be precipitated by organic brain disorders. While the association between hyperthyroidism and mania is well described, mania or hypomania precipitated by hypothyroidism is rare. The authors present late-onset bipolar disorder in a 72-year-old woman presenting with mania and psychosis, which appear to have been precipitated by autoimmune hypothyroidism. This case shows the importance of ascertaining the thyroid status in patients with mood and psychotic disorders, especially in elderly patients and in patients lacking prominent signs of thyroid disease.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Hypothyroidism; Psychotic Disorders; Quetiapine Fumarate; Thyroxine

The author relates the case study of a 38-year-old man with schizoaffective disorder (bipolar type) refractory to multiple medications. This patient had a long history of psychiatric illness and had been hospitalized at least 15 times because of aggression, hostility, and psychosis. Two separate trials of risperidone and olanzapine resulted in adverse effects, including possible neuroleptic malignant syndrome. Quetiapine, as part of combination therapy, led to substantial reductions in the patient's schizoaffective disorder symptoms and problematic behaviors. The patient tolerated quetiapine and did not experience any adverse effects. Quetiapine may be a suitable treatment option in patients with schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Humans; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Violence

Quetiapine is a dopamine D2 and serotonin 5-HT2 antagonist with antipsychotic and mood-stabilizing properties. Recent studies suggest that higher doses of quetiapine combine superior therapeutic efficacy with good tolerability. We present five patients, in whom treatment with higher doses of quetiapine was associated with constipation. Our observations raise the question of dose-dependent constipation under treatment with quetiapine.

Topics: Adult; Antipsychotic Agents; Constipation; Depression; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Although most patients treated for first-episode schizophrenia will experience considerable improvement with initial antipsychotic therapy, a subgroup experiences significant ongoing positive symptoms. Clozapine has unique efficacy in improving treatment-resistant patients with chronic schizophrenia, but its role in the treatment of first-episode patients remains unclear. A standardized treatment algorithm was implemented in our First Episode Psychosis Program, with patients receiving 2 trials with 2 second-generation antipsychotics (olanzapine, quetiapine, or risperidone at low, medium, and high doses), followed by a trial of clozapine as early as 25 weeks into the start of their treatment. Patients progress along the algorithm according to their response as defined by clinical rating scales. To date, 123 patients with first-episode schizophrenia have been treated according to the algorithm. Of these, 93 (76%) responded to the first trial of an antipsychotic. Only 7 (23%) of the remaining 30 patients responded to a second antipsychotic trial; 13 of the remaining 23 individuals agreed to a trial of clozapine. We compared the clozapine-treated group with a group of 9 patients who refused clozapine and chose to continue the same antipsychotic treatment as before. Subjects who received clozapine experienced a mean Brief Psychiatric Rating Scale change of 19 points (from 53.5 to 34.5) and a change in the Clinical Global Inventory severity rating from 5.4 to 3.5 (from severely ill to mildly ill); those who refused clozapine had a 2-point increase in mean Brief Psychiatric Rating Scale (from 53 to 55) and a 0.6-point increase in the mean Clinical Global Inventory severity rating from 5.4 to 6 (remaining markedly to severely ill). In clinical practice, there is a hesitancy to switch individuals to clozapine given its side effect profile and position as treatment of "last resort." The present findings suggest that clozapine may have an important role in the early treatment of first-episode patients whose psychosis does not remit with other second-generation antipsychotics during the first months of treatment.

Topics: Adolescent; Adult; Algorithms; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Resistance; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antimanic Agents; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Torticollis; Valproic Acid

Topics: Adrenal Gland Neoplasms; Adult; Antipsychotic Agents; Diagnosis, Differential; Dibenzothiazepines; False Positive Reactions; Female; Humans; Neurilemmoma; Normetanephrine; Pheochromocytoma; Psychotic Disorders; Quetiapine Fumarate

There are limited data regarding the use of atypical antipsychotic medications in pregnancy. The objectives of the current study were to quantify placental permeability to antipsychotic medications and to document obstetrical outcomes for women taking these agents proximate to delivery.. The authors conducted a prospective observational study of women treated with an atypical antipsychotic or haloperidol during pregnancy. Maternal and umbilical cord plasma samples collected at delivery were analyzed for medication concentrations. Placental passage was defined as the ratio of umbilical cord to maternal plasma concentrations (ng/ml). Obstetrical outcome was ascertained through maternal reports and reviews of obstetrical records.. Fifty-four pregnant women with laboratory-confirmed antipsychotic use proximate to delivery were included in the analysis. Complete maternal-infant sample pairs were available for 50 participants. Placental passage ratio was highest for olanzapine (mean=72.1%, SD=42.0%), followed by haloperidol (mean=65.5%, SD=40.3%), risperidone (mean=49.2%, SD=33.9%), and quetiapine (mean=23.8%, SD=11.0%). There were tendencies toward higher rates of low birth weight (30.8%) and neonatal intensive care unit admission (30.8%) among neonates exposed to olanzapine.. All four antipsychotics demonstrated incomplete placental passage. Quetiapine demonstrated the lowest placental passage of the medications studied. These novel data provide an initial quantification of the placental passage of antipsychotics and fetal exposure in humans, demonstrating significant differences between individual medications.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Fetal Blood; Haloperidol; Humans; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Maternal-Fetal Exchange; Olanzapine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone

The objective of the present study was to investigate the effect of age, gender, and various comedications on the pharmacokinetics of quetiapine in a naturalistic setting.. In total, 2111 serum samples analyzed for quetiapine during the period from June 2001 to December 2004 were included in the study. The samples had been collected for routine therapeutic drug monitoring purposes from 1179 patients treated with quetiapine. A log-linear mixed model was used to identify factors influencing the dose-corrected quetiapine serum concentration, expressed as the quetiapine concentration-to-dose (C/D) ratio. Variables included in the analysis were age, gender, and concomitant treatment with a total of 41 drugs most often used in combination with quetiapine.. Age >or= 70 years (p = .001) and comedication with alimemazine (p = .002), fluvoxamine (p = .001), citalopram/escitalopram (p = .041), or clozapine (p < .001) significantly increased the serum concentrations of quetiapine, while age < 18 years (p = .044) and comedication with lamotrigine (p = .024), levomepromazine (p = .011), oxazepam (p < .001), or carbamazepine (p < .001) significantly decreased the serum concentrations. The effects were most pronounced for fluvoxamine (+159%), clozapine (+82%), age >or= 70 years (+67%), and carbamaze-pine (-86%). In 18% of the samples, the daily dose exceeded the currently recommended maximum of 800 mg/day.. Due to the increased serum levels of quetiapine, a lower dose than usual should be considered when quetiapine is administered to elderly patients and to patients comedicated with clozapine or fluvoxamine. As the inducing effect of carbamazepine on quetiapine metabolism is very potent, cotreatment with carbamazepine cannot be recommended. On the basis of our data and pharmacokinetic considerations, the majority of drugs commonly used in psychiatry can safely be given in combination with quetiapine.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Carbamazepine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Female; Fluvoxamine; Humans; Lamotrigine; Male; Methotrimeprazine; Middle Aged; Oxazepam; Psychotic Disorders; Quetiapine Fumarate; Triazines

We examined the reliability and construct validity of the 5-Item Arizona Sexual Experience Scale (ASEX) in patients with schizophrenia or schizoaffective disorder. In addition, we assessed the performance of two 1-item screening questions to detect sexual dysfunction as defined by a cut-off scoring criteria of sexual dysfunction for the ASEX. One question was a general question about any side effects. The second question asked specifically about sexual dysfunction. Altogether 247 participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder provided data at a single interview. Results indicated that the ASEX has good internal consistency and construct validity for the patients with schizophrenia and schizoaffective disorder. The point-biserial correlations and logistic regression found a high degree of agreement between the one-item specific screening question for sexual dysfunction and the ASEX. Overall, sensitivity (85%), specificity (63.7%), and positive (83%) and negative (67.1%) predictive values for the specific one-item screening question were satisfactory. The single general side effect question performed poorly (sensitivity=11.3%; specificity=92.5%; positive predictive value=76%; negative predictive value=33%). The current findings demonstrate the highly acceptable psychometric properties of the ASEX in patients with schizophrenia or schizoaffective disorder. In addition, a specific one-item screening question is of clinical utility in patients with schizophrenia or schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Dibenzothiazepines; Female; Humans; Interview, Psychological; Male; Middle Aged; Olanzapine; Psychometrics; Psychotic Disorders; Quetiapine Fumarate; Reproducibility of Results; Risperidone; Schizophrenia; Sexual Dysfunction, Physiological

To determine whether atypical antipsychotic polytherapy is a risk factor for drug treatment for extrapyramidal side-effects (anti-EPS drugs) and whether the risk is attributable to antipsychotic dose.. We studied Iowa Medicaid beneficiaries aged 18-64 years with an active atypical and no conventional antipsychotic on January 1, 2001. The association of atypical antipsychotic polytherapy with anti-EPS drug treatment was determined. Multiple logistic regression was utilized to adjust for covariates in two models, the first adjusting for age, sex and the specific antipsychotic(s) prescribed, and the second also adjusting for doses.. Among 4400 patients, the unadjusted odds of anti-EPS treatment were increased two-fold with polytherapy. Polytherapy remained a risk factor in the first model (OR 1.5, 95% CI 1.1-2.0), but not after adjusting for doses (OR 1.0, 95% CI 0.7-1.4).. Atypical antipsychotic polytherapy is a risk factor for anti-EPS drug treatment, apparently because of higher cumulative doses.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cross-Sectional Studies; Delayed-Action Preparations; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Iowa; Male; Mathematical Computing; Medicaid; Middle Aged; Models, Statistical; Olanzapine; Product Surveillance, Postmarketing; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Risk Factors; Risperidone; Statistics as Topic

Topics: Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dibenzothiazepines; Drug Administration Schedule; Drug Resistance; Humans; Mental Disorders; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Selection Bias; Thiazoles; Treatment Outcome

Massive elevations of serum creatine kinase (CK) can occur in a significant number of patients treated with neuroleptics in the absence of neuroleptic malignant syndrome (NMS). We report two cases of CK-elevations associated with quetiapine treatment, which disappeared after drug discontinuation. To our knowledge, case number one is the first case of quetiapine-induced CK elevation in a neuroleptic-naïve patient. We thus suggest CK assessment when myalgia occurs with neuroleptic treatment.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Creatine Kinase; Depressive Disorder, Major; Dibenzothiazepines; Humans; Male; Mianserin; Mirtazapine; Olanzapine; Pain; Psychotic Disorders; Quetiapine Fumarate

A 75-year-old white female with schizoaffective disorder was admitted to an inpatient psychiatry unit for uncooperativeness in refusing to take scheduled medications. She complained of anticholinergic adverse effects and had abnormal involuntary movements in the oral/buccal region. The patient had been prescribed six psychotropic medications (i.e., thiothixene, lithium, divalproex sodium, amitriptyline, benztropine, and trazodone effects. The treatment team determined that the patient was noncompliant and experienced the effects of polypharmacy. She had been prescribed two mood stabilizers and suffered from anticholinergic adverse effects and the movement disorder tardive dyskinesia (TD). Four medications were discontinued: thiothixene, amitriptyline, lithium, and benztropine. Quetiapine, a second-generation antipsychotic, was recommended, with a daily titration schedule to reach a target dose of 600 mg per day in divided doses. This agent has less propensity to cause movement disorders compared with first-generation antipsychotics. All medications with additive anticholinergic properties also were discontinued. Lithium was stopped secondary to subtherapeutic levels and potential drug interactions. The pharmacist educated the inpatient team on the additive anticholinergic effects of each medication, reduced the total number of medications prescribed, and assisted in appropriate conversion to quetiapine to reduce TD symptoms.

Topics: Aged; Antipsychotic Agents; Cholinergic Antagonists; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Neuroleptic Malignant Syndrome; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Treatment Refusal

Topics: Administration, Oral; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Haloperidol; Humans; Injections; Psychotic Disorders; Quetiapine Fumarate; Research Design; Sample Size; Schizophrenia; Treatment Outcome

Evaluate sexual dysfunction, as measured by the Arizona Sexual Experience Scale (ASEX), in olanzapine-, quetiapine-, and risperidone-treated outpatients with schizophrenia or schizoaffective disorder.. The sexual functioning of 238 outpatients (age> or =18 years) with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine (n=57), olanzapine (n=94), or risperidone (n=87) was evaluated with a one-time rating of the ASEX. The dose range for each treatment group was 5 to 40 mg/day (M=16.6 mg/day, SD=7.4) for olanzapine; 1 to 8 mg/day (M=3.9 mg/day, SD=1.6) for risperidone; and 50 to 900 mg/day (M=376.8 mg/day, SD=213.4) for quetiapine. Antipsychotic group designation was based on medication treatment at study entry (i.e., non-random assignment). Participant characteristics were collected to test for treatment group differences and for potential associations with severity of sexual dysfunction. The primary data analysis was a mixed linear model analysis of covariance with age, gender, and presence/absence of antidepressant known to cause sexual dysfunction included as covariates.. There was a significant treatment effect on severity of sexual dysfunction, as measured by ASEX total scores (p=.04). The adjusted average ASEX total scores were lower in the quetiapine (M=17.80) than in the risperidone (M=19.69) or olanzapine (M=20.34) groups. Individual comparisons of the treatments on adjusted average ASEX total scores indicated a significant difference between olanzapine and quetiapine (p=.04), but no difference between risperidone and quetiapine (p=.17) or olanzapine and risperidone (p=.76).. Quetiapine was associated with less severe sexual dysfunction than olanzapine and risperidone (albeit the effect between risperidone and quetiapine was not statistically significant). Olanzapine and risperidone were associated with a comparable degree of sexual dysfunction. Patients in all three treatment groups, nonetheless, experienced a moderately high degree of sexual dysfunction. Because the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Outpatients; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Severity of Illness Index; Sexual Dysfunction, Physiological

Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

Topics: Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Dibenzothiazepines; Humans; Leptin; Lipids; Lipoproteins; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Vision Disorders

Priapism is a "persistent erection not accompanied by sexual desire or stimulation, usually lasting more than six hours and typically involving only the corpora cavernosa." Here we report on a gay male patient from our HIV/AIDS mental health clinic who developed serious priapism on quetiapine and recreational amphetamine. Gay men are at high risk for amphetamine use, and as such, this potential association between priapism, quetiapine, and amphetamine use should be considered in making prescription decisions with these patients.

Topics: Amphetamine; Amphetamine-Related Disorders; Antipsychotic Agents; Comorbidity; Depressive Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; HIV Seropositivity; Homosexuality, Male; Humans; Male; Mianserin; Middle Aged; Mirtazapine; Priapism; Psychotic Disorders; Quetiapine Fumarate

In this case report we describe a patient who suffered brainstem bleeding mainly in the pons and mesencephalon leading to locked-in syndrome. During rehabilitation she suffered psychotic symptoms of threatening character. Due to location of the lesion and the coincidental appearance of the bleeding, we diagnosed an organic psychosis. After treatment with the atypical neuroleptic drug Quetiapine, the symptoms decreased, facilitating the patient's rehabilitation course.

Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Brain Stem; Cerebral Hemorrhage; Delusions; Depressive Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Hypertension; Mianserin; Middle Aged; Mirtazapine; Neurologic Examination; Psychotic Disorders; Quadriplegia; Quetiapine Fumarate; Tomography, X-Ray Computed

To determine whether psychiatrically stable patients with a history of drug-induced psychosis could be successfully weaned off their antipsychotic drug, we offered consecutive Parkinson disease (PD) patients on quetiapine or clozapine, who were free of any on-going psychosis, to be slowly weaned off their antipsychotic drug. Before the study was aborted 6 PD patients (mean age, 78 years) with an average antipsychotic exposure of 20 months (5 on quetiapine, 1 on clozapine) were enrolled. After the antipsychotic agent was discontinued, psychosis recurred in 5 of 6 patients. In 3 patients the "rebound psychosis" was worse than the original psychotic episode and required subsequent higher antipsychotic medication doses.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Parkinson Disease; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Time Factors

Topics: Adolescent; Antipsychotic Agents; Citalopram; Depressive Disorder; Dibenzothiazepines; Drug Synergism; Drug Therapy, Combination; Female; Humans; Obesity; Psychotic Disorders; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Weight Gain

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Hypothyroidism; Psychotic Disorders; Quetiapine Fumarate

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate

Antipsychotic-induced extrapyramidal side effects have a negative impact on treatment for mental illness. Acute dystonic reactions are uncomfortable and frightening to the patient, and often lead to early discontinuation of drug therapy and worsened long-term outcome. The lower propensity of the atypical antipsychotic agents to cause extrapyramidal symptoms (EPS) has been associated with multiple benefits, including improved adherence. The authors describe a 57-year-old male patient who was in the treatment refractory unit. This patient exhibited extreme sensitivity to antipsychotic agents, experiencing acute dystonic reactions with quetiapine and olanzapine, in addition to older typical antipsychotic agents. The patient has not experienced acute EPS since therapy with aripiprazole was initiated. Further complicating this patient's course is his unusual sensitivity to experiencing dystonic reactions. We have observed acute dystonias in the absence of antipsychotic treatment and in the context of seizure activity (or paroxysmal dyskinetic activity). The true etiology of the latter dystonic activity has not been completely determined due to the patient's unwillingness to cooperate with invasive testing. None of the gene variations tested (CYP2D6 phenotype, two dopamine D2 receptor variants and one D3 receptor variant) appeared to explain the patient's vulnerability to acute dystonic reactions.

Topics: Anticonvulsants; Antipsychotic Agents; Chronic Disease; Cytochrome P-450 CYP2D6; Dibenzothiazepines; Dystonia; Genotype; Humans; Male; Middle Aged; Phenytoin; Psychotic Disorders; Quetiapine Fumarate; Seizures; Valproic Acid

There are few real life independent comparative studies of atypical antipsychotics. We prospectively examined five commonly used atypical antipychotics in the UK, without support from the pharmaceutical industry.. Prospective naturalistic systematic clinical evaluation. Patients being newly prescribed atypical anti-psychotics over a one year period were assessed by psychiatrists at initiation and after six months treatment using five outcome measures: clinical global impression; positive and negative psychotic symptoms; drug related side effects; and quality of life.. 373 patients participated in total. Olanzapine and risperidone produced statistically significant reductions in all ratings at six months. Amisulpride, clozapine, and quetiapine were also studied. There was limited variance between the different drugs, although some sample sizes were small.. Atypical anti-psychotics were found to be clinically effective, and produced similar outcomes. Routine monitoring of outcomes in psychiatry is feasible.

Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Probability; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risk Assessment; Risperidone; Severity of Illness Index; Statistics, Nonparametric; Sulpiride; Treatment Outcome

The possibility that low-dose antipsychotic treatment is associated with increased risk of cerebrovascular events (CVEs) in elderly patients with dementia has been raised. The objective was to determine whether risperidone is associated with an increased risk of CVEs relative to other commonly considered alternative treatments.. An analysis of Medicaid data from 1999 to 2002, representing approximately 8 million enrollees from multiple states, was conducted. The primary outcome was the incidence of acute inpatient admission for a CVE within 3 months following initiation of treatment with atypical antipsychotics (risperidone, olanzapine, quetiapine, or ziprasidone), haloperidol, or benzo-diazepines.. Descriptive analyses found similar rates of incident CVEs across evaluated agents. Multivariate analyses found no differences in comparisons of risperidone with olanzapine or quetiapine. Risperidone and other antipsychotics as a group were also not associated with a higher odds ratio (OR) of incident CVE than either haloperidol or benzodiazepines. With risperidone as the reference group: olanzapine, OR = 1.05, 95% CI 0.63-1.73; quetiapine, OR = 0.66, 95% CI 0.23-1.87; haloperidol, OR = 1.91, 95% CI 1.02-3.60; benzodiazepines, OR = 1.97, 95% CI 1.30-2.98. With benzodiazepines as the reference group, the OR of incident CVE for all antipsychotics as a class was 0.49, 95%CI 0.35-0.69.. This study found no significant difference in the incidence of CVEs between patients taking risperidone and those taking other atypical antipsychotics. Risperidone and all atypical antipsychotics were not associated with higher risk than two common treatment alternatives (haloperidol and benzodiazepines). These findings do not support the conclusion that risperidone is associated with a higher risk of CVE than other available treatment alternatives. The data also suggest that patient characteristics other than antipsychotic use are more significant predictors of CVEs. Given the relatively low rates of incident CVEs, a larger sample of patients with groups closely balanced on a wide spectrum of potential risk factors could provide a more precise assessment of risk.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cohort Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Haloperidol; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Thiazoles

Quetiapine, an atypical antipsychotic, is effective for psychosis in younger patients, with limited adverse effects reported. This open-label naturalistic study was conducted to assess the 4-week efficacy and safety of quetiapine for treatment of geriatric psychosis. Clinical efficacy was evaluated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments before and after 4 weeks of quetiapine treatment. The sample population consisted of 100 geropsychiatric inpatients with psychosis, with the therapeutic evaluation completed by 91. Eighty-one of these 91 patients (89.0%) experienced mild-to-substantial improvement, as determined from the CGI-I. Further, a mean reduction in BPRS score of 39.5% (from baseline) was also determined. The mean daily dose of quetiapine for the fourth week was 276.1 177.2mg/day (range 50-800). Higher quetiapine dosages were administered for patients with functional psychoses compared to an analogous group with organic mental disorders. The most common adverse effects were somnolence (30.0%), lower-limb weakness (28.0%) and dizziness (27.0%). Body weight and fasting triglyceride were significantly elevated after quetiapine treatment (2.2% and 8.9% from baseline, respectively). Based on the results of this study, it appears that quetiapine is an efficacious and safe treatment for geriatric inpatients with psychosis, however, there is a wide dosing range and optimal dosage is diagnosis-dependent.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Brief Psychiatric Rating Scale; Delusions; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Geriatric Assessment; Humans; Male; Mood Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Plasma prolactin concentration was measured in patients with schizophrenia and schizoaffective disorders receiving therapy with risperidone, olanzapine, and quetiapine and compared with the corresponding parameter in patient receiving typical neuroleptic drug haloperidol. We evaluated the specific effects of the test drugs on prolactin concentration in men and women.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Haloperidol; Humans; Immunoenzyme Techniques; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sex Factors

Topics: Antipsychotic Agents; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Administration Schedule; Drug Tolerance; Humans; Meta-Analysis as Topic; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Retrospective Studies

As a follow-up to our previous study of clozapine, medical records of a state psychiatric hospital were reviewed for patients who were prescribed an atypical antipsychotic. From that sample, demographic and clinical data were obtained for individuals with an initial score of 35 or greater on the Brief Psychiatric Rating Scale (BPRS), and at least two additional successive monthly BPRS ratings. A total of 100 patients met the criteria. Most received either olanzapine (46%) or risperidone (36%), with few administered quetiapine (11%) or clozapine (7%). Most also received adjunctive medications, including conventional antipsychotics, anticonvulsants/mood stabilizers, antidepressants, and antiparkinsonian agents. The number of patients whose BPRS total scores decreased by 20% or more from baseline was significantly greater for those who received olanzapine than those who received risperidone. However, there was no difference between the two antipsychotics in the number of patients who maintained that degree of improvement, in the average latency to achieve that decrease (1.67 and 1.47 months, respectively), or the average length of stay (LOS; 332 and 376 days, respectively). These results indicate a modest therapeutic advantage of olanzapine compared to risperidone, and a substantial degree of polypharmacy in the use of atypical antipsychotics. This uncontrolled "real-world" evaluation supports data from controlled clinical trials, showing that either risperidone or olanzapine would be a reasonable first choice in patients with treatment-resistant schizophrenia, with the decision based on the least adverse side effect profile and economic constraints. When compared to our previous clozapine study, we confirm a slight advantage for the effectiveness of clozapine in the treatment of this refractory population.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Female; Hospitals, Psychiatric; Hospitals, State; Humans; Length of Stay; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Topics: Aged; Amisulpride; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Sulpiride

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Huntington Disease; Male; Psychotic Disorders; Quetiapine Fumarate

Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics.. Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone.. Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31).. Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzazepines; Benzodiazepines; Carbon Radioisotopes; Clozapine; Corpus Striatum; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D1; Receptors, Dopamine D2; Risperidone; Schizophrenia; Tomography, Emission-Computed; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Cataract; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

To assess the pharmacokinetics and tolerability of quetiapine in elderly patients with selected psychotic disorders.. This was a multicentre, open-label, 27-day, rising multiple-dose trial. Descriptive statistics summarised plasma quetiapine concentrations and pharmacokinetic parameters by trial day. A two-way analysis of variance was used to evaluate all pharmacokinetic parameters, and 90% confidence intervals of the mean differences were calculated.. Antipsychotic drugs taken prior to the study period were discontinued on day 1. Quetiapine treatment began on day 3. Doses were increased stepwise, starting at 25mg three times daily and reaching 250mg three times daily by day 21.. Twelve patients (age 63-85 years) with schizophrenia, schizoaffective disorder or bipolar disorder.. Key assessments included quetiapine plasma concentrations, and neurological and safety evaluations. Under steady-state conditions, the 100 and 250mg doses of quetiapine were not significantly different in terms of dose-normalised area under the plasma concentration-time curve within an 8-hour dose administration interval, or in dose-normalised minimum plasma concentration (C(min)) at the end of a dose administration interval. The morning C(min) values for the seven discrete dose amounts evaluated also increased linearly with dose. The apparent oral clearance, volume of distribution and half-life did not change as a function of dose. There were no serious adverse events. The most common adverse events were postural hypotension (n = 6), dizziness (n = 5) and somnolence (n = 4).. While quetiapine was well tolerated at doses up to 250mg three times daily, the potential for reduced clearance, as well as the adverse effects of postural hypotension and dizziness, indicated that quetiapine should be introduced at lower doses and titrated at a relatively slower rate in patients > or =65 years.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Blood Pressure; Dibenzothiazepines; Electrocardiography; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Marijuana Abuse; Middle Aged; Pilot Projects; Psychotic Disorders; Quetiapine Fumarate

The results concerning therapeutic drug monitoring of Quetiapin concentration in 152 in-patients will be presented.. In addition to measuring the serum concentration of Quetiapin standardized patient data were collected and the clinical history assessed by the Brief Psychiatric Rating Scale (BPRS).. A significant positive correlation of the serum concentration and the daily dosage was found. Co-medication with the CYP 3A4 inhibitor Nefazodon was associated with an increase in the serum concentration without any adverse interactions occurring.. While a correlation of dosage and effect could be shown with Quetiapin, inter- and intraindividual differences could be observed. Drug monitoring therefore seems useful in clinical setting and is recommended.

Topics: Adult; Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Female; Humans; Male; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Statistics as Topic; Triazoles

Therapeutic drug monitoring (TDM) has been established at BKH Augsburg (psychiatric district hospital) since January 2001. According to Olanzapine product information the following illustration shows the evaluation (n = 216) of various parameters of the TDM requirements of Olanzapine.. Items examined include "classification according to diagnoses", "reason for requirement", "severity of disease", "therapeutic effect" and "side-effects". In addition, serum concentration, daily dosage, clinical assessment (Brief Psychiatric Rating Scale), age, height and weight of patients will be presented.. Clearly sick patients, 52 % of them between 20 and 30 years old, were less compliant and achieved only a moderate therapeutic effect.. TDM is mainly assessed to control compliance. However, more specific and more personalized TDM would be more useful.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Treatment Outcome

As evidence of a biologic determinant of schizophrenia has been elaborated, an interest in the relationship between schizophrenia and autoimmune disorders has become increasingly more developed over the last decade. Pedigree analysis has shown that schizophrenia, like autoimmune disorders, is likely a heritable phenomenon, and a genetic liability in this disorder is hardly disputed. Research has indicated that physiologic connections between IFN-gamma and TNF-alpha are suggestive of a connection between the symptoms associated with schizophrenia and those of hypoglycemic events in IDDM. Autoimmune pathogeneses of schizophrenia have been hypothesized; however, the clinical delineation of a potentially corresponding subset of patients is rarely addressed.. We treated a 22-year-old white female who carried the concomitant diagnoses of Schizophrenia, IDDM, and Hypothyroidism with quetiapine and risperidone on an acute basis at our inpatient facility, and observed an apparent resolution of her brittle diabetes with the successful treatment of her psychotic disorder.. The well documented link between antipsychotic agents and changes in blood glucose may be of benefit in a subset of patients who suffer from both psychotic and diabetic disorders.

Topics: Adult; Antipsychotic Agents; Blood Glucose; Diabetes Mellitus, Type 1; Dibenzothiazepines; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Chromatography, High Pressure Liquid; Dibenzothiazepines; Drug Therapy, Combination; False Positive Reactions; Female; Humans; Immunoassay; Nortriptyline; Psychotic Disorders; Quetiapine Fumarate

The authors present the case of a man who was hospitalized after claiming that he was about to become a serial killer. The patient presented with extensive written homicidal fantasies and homicidal intentions without evidence of actual homicidal acts. In addition to routine assessments, hospital staff members used case conferences, psychological testing, outside forensic consultation, and a forensic review process to make decisions regarding diagnosis, treatment planning, and discharge. The patient was discharged after 8 months of inpatient treatment and was apparently free of homicidal impulses or symptoms of severe mental illness. A 2-year court commitment allowed for the enactment and potential enforcement of a discharge plan that was endorsed by the patient, the hospital, and community care providers. The authors review diagnostic and risk management issues. Comparisons with known features of typical serial killers are made.

Topics: Adult; Anticonvulsants; Commitment of Mentally Ill; Dibenzothiazepines; Fantasy; Forensic Psychiatry; Homicide; Hospitalization; Hospitals, Psychiatric; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Seizures; Self Disclosure

The authors describe here the clinical outcomes of quetiapine treatment in nine patients with dementia with Lewy bodies (DLB) who manifested psychotic symptoms and aggressive behavior. Patients who had a score of 3 or higher on any of the three items of the Neuropsychiatric Inventory (NPI), agitation/aggression, hallucinations, and delusions, were given quetiapine 25-75 mg/day. Each patient's clinical status was assessed at baseline and after 4 and 8 weeks of treatment by using the NPI, Mini-Mental State Examination (MMSE), and Simpson-Angus Scale (S-A). Five of nine patients had a positive response with a decline of more than 50% in the sum of scores for three items of the NPI. The other three patients withdrew from quetiapine treatment due to somnolence or orthostatic hypotension. The remaining patient exhibited no clinically significant change in the NPI score. The S-A scale was not affected by quetiapine treatment in any patient. These findings suggest that quetiapine may be effective in treating psychotic symptoms and disruptive behavior in some patients with DLB. Further placebo-controlled, randomized, double-blind trials with this drug are needed to confirm this observation.

Topics: Aged; Aged, 80 and over; Aggression; Dibenzothiazepines; Humans; Lewy Body Disease; Male; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate

To evaluate the long-term efficacy and tolerability of quetiapine for psychosis among parkinsonian patients, a retrospective analysis of all parkinsonian patients taking quetiapine for psychosis in a single movement disorders center was carried out. Demographic data, including type and severity of psychosis, presence of dementia, treatment response, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores and Hoehn and Yahr (H&Y) scale were obtained. One hundred six parkinsonian patients with a mean age of 76.6 years were on an average levodopa (L-dopa) dose of 415 mg/d. Seventy-eight of 106 (74%) remained on quetiapine for a mean duration of 15 months at an average dose of 60 mg per day. Eighty-seven (82%) patients had partial or complete resolution of their psychosis whereas 19 (18%) patients had no improvement on quetiapine. Motor worsening was noted in 34 (32%) patients but was uncommonly sufficient to warrant quetiapine discontinuation. More quetiapine non-responders were noted to be demented, delusional, and experienced threatening psychosis but only the presence of dementia remained significant on multivariate analysis (OR = 11.6; 95% CI = 1.4-92.9). Also, patients who developed motor worsening while on quetiapine tended to be more demented (P = 0.07).

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Drug Tolerance; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Levodopa; Male; Outcome Assessment, Health Care; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Severity of Illness Index

Topics: Antipsychotic Agents; Dibenzothiazepines; Electroencephalography; Equipment Failure; Female; Humans; Long QT Syndrome; Middle Aged; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index

To report a case of seizures in a patient with Alzheimer disease, who was receiving quetiapine for psychoses.. A 75-year-old white man with Alzheimer disease was observed to have seizures while receiving quetiapine 500 mg/d and carbamazepine 200 mg/d. He had been taking quetiapine for 18 months prior to the event. No other toxic, metabolic, or anatomic abnormalities were identified to explain the seizures. After cessation of quetiapine treatment, the patient remained seizure free. An objective causality assessment revealed that the adverse drug reaction was possible.. The patient was taking a relatively high dose of quetiapine. An increased risk of seizures has been associated with Alzheimer disease. Using a relatively high dose of quetiapine may have resulted in seizures in our patient with Alzheimer disease.. As with other antipsychotics, quetiapine should be used cautiously in elderly patients with conditions that can lower the seizure threshold, and special monitoring should be performed for this serious adverse effect.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Carbamazepine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Seizures

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

Topics: Anticonvulsants; Antipsychotic Agents; Diazepam; Dibenzothiazepines; Drug Therapy, Combination; Haloperidol; Humans; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Secondary Prevention

Topics: Aged; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Electrocardiography; Female; Humans; Long QT Syndrome; Psychotic Disorders; Quetiapine Fumarate; Ventricular Premature Complexes

In the present open prospective study the effects of quetiapine were investigated in two elderly patients with parkinsonism and psychosis. Treatment induced a marked antipsychotic effect that coincided with an improvement of general motor functioning. These findings support the idea that quetiapine may be preferentially of use in the elderly with parkinson's disease and psychotic symptoms.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Among atypical antipsychotics, quetiapine is characterized by a lower incidence of aggravation of parkinsonism due to its lower affinity to D 2. In this study, the effect of quetiapine fumarate (quetiapine) on antiparkinsonian-drug-induced psychosis (e.g. hallucination and delusion) in patients with Parkinson's disease was examined. Ten patients with antiparkinsonian-drugs-induced psychosis were enrolled in this study. The average age of the patients was 69 years and the mean duration of illness was 7 years and 5 months. Psychosis and parkinsonism in these patients were assessed by the Japanese version of PANSS (Positive and Negative Symptom Scale) and UPDRS (Unified Parkinson's Disease Rating Scale) before and during administration of quetiapine, respectively. During the assessment of the effect of quetiapine, the antiparkinsonian drugs that the patients were taking were unchanged. In nine out of the 10 patients, psychotic symptoms disappeared following administration of a relative small dose of quetiapine. No remarkable aggravation of parkinsonism was observed. The present results indicate that quetiapine is an useful drug for treating antiparkinsonian-drug-induced psychosis in the patient with Parkinson's disease.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Psychotic Disorders; Quetiapine Fumarate

The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels.. The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses.. Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations.. It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Haloperidol; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Triglycerides; Weight Gain

Novel antipsychotics (clozapine, risperidone, olanzapine, quetiapine) are effective in treating psychotic symptoms, also in neurological disease. Hyperprolactinemia is a side effect related to antipsychotics that can cause galactorrhea, gynecomastia, amenorrhea, anovulation, impaired spermatogenesis, decreased libido and sexual arousal, impotence, and anorgasmia, consequent to removal of tonic dopaminergic inhibition of prolactin secretion via hypothalamic dopaminergic receptor blockade in the tuberoinfundibolar tract. Hyperprolactinemia occurs more frequently during treatment with risperidone and olanzapine compared with clozapine and quetiapine. The therapeutic algorithm to antipsychotic-relatedhyperprolactinemia is the following: reduction in antipsychotic dose, addition of cabergoline, bromocriptine, amantadine, and/or switch to another antipsychotic. We propose switching to quetiapine in symptomatic hyperprolactinemia related to antipsychotics and describe five cases.

Topics: Adolescent; Adult; Antipsychotic Agents; Citalopram; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Neurosarcoidosis is a rare disorder in which psychosis and dementia may occur. They usually appear subsequently to the diagnosis of pulmonary sarcoidosis. We report on a 39-year-old patient who presented with long-term decline and acute onset of psychosis and delirium, and who was found to have neurosarcoidosis.

Topics: Acute Disease; Adult; Antipsychotic Agents; Brain; Brain Diseases; Cognition Disorders; Diagnosis, Differential; Dibenzothiazepines; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Psychotic Disorders; Quetiapine Fumarate; Sarcoidosis; Tomography, X-Ray Computed

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Psychotic Disorders; Quetiapine Fumarate

Quetiapine fumarate (Seroquel) is an atypical antipsychotic agent approved for the treatment of psychosis. It is extensively metabolized by the CYP450 3A4 isozyme. The principal aim of the study was to investigate the effect of multiple doses of cimetidine, a nonspecific P450 inhibitor, on the steady-state pharmacokinetics of quetiapine. Thirteen patients (seven completers) with selected psychotic disorders received escalating doses of quetiapine from 25 to 150 mg three times daily on days 3 to 8 and were then maintained at 150 mg three times daily until day 19. Cimetidine (400 mg) was initiated on the afternoon of day 15 and administered three times daily with every dose of quetiapine thereafter. Quetiapine plasma concentrations were measured before and after cimetidine coadministration, and quetiapine pharmacokinetic parameters were calculated. Of the 13 men who entered the study, seven completed it. A slight increase in quetiapine plasma levels and reduction in oral clearance were observed after cimetidine coadministration. No serious adverse events were observed during quetiapine treatment. No clinically relevant alterations in quetiapine pharmacokinetics were observed after cimetidine coadministration in patients with psychotic disorders.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cimetidine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Humans; Male; Metabolic Clearance Rate; Middle Aged; Mixed Function Oxygenases; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Family Practice; Humans; Multicenter Studies as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Cost of Illness; Dibenzothiazepines; Humans; Nursing Homes; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; United States

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Leukocyte Count; Leukopenia; Psychotic Disorders; Quetiapine Fumarate

The hypothesis provides the justification for the clinical trial. It is antecedent to the trial and establishes the trial's direction. Hypothesis testing is the most widely employed method of determining whether the outcome of clinical trials is positive or negative. Too often, however, neither the hypothesis nor the statistical information necessary to evaluate outcomes, such as p values and alpha levels, is stated explicitly in reports of clinical trials. This article examines 5 recent studies comparing atypical antipsychotics with special attention to how they approach the hypothesis and hypothesis testing. Alternative approaches are also discussed.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Humans; Olanzapine; Periodicals as Topic; Pirenzepine; Psychotic Disorders; Publishing; Quetiapine Fumarate; Reproducibility of Results; Research Design; Risperidone; Schizophrenia; Terminology as Topic

Although quetiapine is the antipsychotic of choice for the psychosis associated with Parkinson's disease (PD) and often is also helpful for sleep, we report two cases of quetiapine-induced extrapyramidal side effects. The patients described were unusual in their frailty and severity of illness and may not represent the majority of patients with PD.

Topics: Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Ocular Motility Disorders; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

Topics: Adolescent; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Depressive Disorder; Dibenzothiazepines; Fluoxetine; Hallucinations; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

The assumption that psychotic patients assigned to placebo in clinical trials of antipsychotics are exposed to substantial morbidity and mortality is not based on data about what actually happens to such patients. This study assesses symptoms and risks of suicide and suicide attempts in psychotic patients assigned to receive placebo in clinical trials.. The authors used the Food and Drug Administration database to assess suicides, suicide attempts, and psychotic symptom reduction in clinical trials of three new antipsychotics.. Among 10,118 participating patients, 26 committed suicide and 51 attempted suicide. Rates of suicide and attempted suicide did not differ significantly between the placebo-treated and the drug-treated groups. Annual rates of suicide and attempted suicide based on patient exposure years were 1.8% and 3.3%, respectively, with placebo; 0.9% and 5.7% with an established antipsychotic; and 0.7% and 5.0% with a new antipsychotic. Symptom reduction was 16.6% with new antipsychotics (N=1,203), 17.3% with established antipsychotics (N=261), and 1.1% with placebo (N=462).. These data may help inform discussions about the use of placebo in antipsychotic clinical trials.

Topics: Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Clinical Trials as Topic; Databases as Topic; Dibenzothiazepines; Drug Approval; Humans; Incidence; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Suicide; Suicide, Attempted; Treatment Outcome; United States; United States Food and Drug Administration

Topics: Aggression; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Cross Reactions; Dibenzothiazepines; False Positive Reactions; Humans; Immunoenzyme Techniques; Male; Psychotic Disorders; Quetiapine Fumarate; Substance Abuse Detection

Neuroleptic-induced tardive dyskinesia, which often appears in middle-aged and older adults early in the course of treatment with low doses of conventional antipsychotics, is 5 to 6 times more prevalent in elderly than in younger patients. In addition to age, other risk factors for tardive dyskinesia include early extrapyramidal symptoms (EPS), cumulative amounts of neuroleptics, duration of neuroleptic treatment, and history of alcohol abuse and/or dependence. The atypical antipsychotics, which have a low liability for EPS, are likely to also have low potential for tardive dyskinesia, despite the paucity of controlled studies. Starting and maintenance doses of the atypical antipsychotics should generally be lower in older than in younger adults.

Topics: Adult; Age Factors; Aged; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Incidence; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone

Side effects of antipsychotic medications are particularly problematic in elderly patients, who experience many age-related changes that may exacerbate medication side effects. Side effects of particular concern in the elderly include anticholinergic reactions, parkinsonian events, tardive dyskinesia, orthostatic hypotension, cardiac conduction disturbances, reduced bone mineral density, sedation, and cognitive slowing. In addition, elderly patients with schizophrenia often have comorbid medical illnesses-such as cardiovascular disease and dementia of the Alzheimer's type-and are thus likely to be taking multiple medications. The effects of polypharmacy must be carefully considered. Patients, caregivers, and family often have different perspectives on side effects. This article addresses the side effects of the currently available antipsychotic medications in light of these concerns.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Movement Disorders; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response.. In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria.. Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding.. Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Depressive Disorder; Dibenzothiazepines; Female; Hospital Records; Humans; Male; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Diabetes Mellitus, Type 2; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Imidazoles; Indoles; Movement Disorders; Psychotic Disorders; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Antipsychotic polypharmacy is a surprisingly frequent occurrence that can be both justified and unjustifed, depending on how it is used. To the extent that this phenomenon has been unrecognized and is not being studied, it is a "dirty little secret." To the extent that careful clinicians have uncovered a useful strategy for boosting the effectiveness of available antipsychotic monotherapies, it represents an opportunity to improve the outcomes of patients with psychotic illnesses.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

There are many difficulties associated with the late stages of Parkinson's disease (PD), but psychosis and agitation may be the most disturbing for both patients and care givers, and often precipitate the pivotal decision for long-term nursing home placement. While the addition of antipsychotic drugs or the withdrawal of antiparkinsonian drugs may improve the behavioral problem, these strategies usually worsen the motor difficulties. Clozapine has been studied in PD for over a decade, and while it appears to be effective, there are safety and tolerability concerns associated with it. In addition, in New Jersey, Medicaid no longer pays for the home blood draws that are required for home-bound patients. This led to a situation in which we had patients who needed to stop clozapine and begin an alternative therapy. Because quetiapine seems particularly well suited to patients with PD based on in vitro and in vivo studies we have begun to try this medication in PD patients who need to stop clozapine. This article reports three case histories of patients with PD, confusion and dopamimetic psychosis who had been previously managed with clozapine and who were successfully switched to quetiapine. At doses from 12.5 to 150 mg/day quetiapine was well tolerated, resulting in behavioral improvement and no real increase in parkinsonism. These case histories raise the possibility that quetiapine may represent a viable alternative to clozapine in PD patients with dopamimetic psychosis and behavioral disturbances.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Confusion; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Humans; Periodicals as Topic; Psychotic Disorders; Publishing; Quetiapine Fumarate; Research Design